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CAS No. : | 5336-08-3 | MDL No. : | MFCD00063241 |
Formula : | C5H8O5 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CUOKHACJLGPRHD-BXXZVTAOSA-N |
M.W : | 148.11 | Pubchem ID : | 111064 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.8 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 3.0 |
Molar Refractivity : | 28.81 |
TPSA : | 86.99 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -8.2 cm/s |
Log Po/w (iLOGP) : | 0.24 |
Log Po/w (XLOGP3) : | -1.41 |
Log Po/w (WLOGP) : | -2.37 |
Log Po/w (MLOGP) : | -2.06 |
Log Po/w (SILICOS-IT) : | -1.07 |
Consensus Log Po/w : | -1.33 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 0.2 |
Solubility : | 233.0 mg/ml ; 1.57 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 0.09 |
Solubility : | 180.0 mg/ml ; 1.22 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | 1.41 |
Solubility : | 3830.0 mg/ml ; 25.9 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.95 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In neat (no solvent) at 25℃; for 3h; Molecular sieve; | Preparation of 2,3,5-tri-O-acetyl-D-ribonolactone (3)14 A mixture of D-ribonolactone 2 (148 mg, 1.0 mmol), Ac2O (1.9 mL, 20 mmol), and 13X/KCl (600 mg) was stirred at 25 °C for 3 h. The catalyst was filtered off through a short pad of Celite and then rinsed with 2-3 mL of EtOAc. The organic phase was concentrated under reduced pressure to give 273 mg(99% yield) of the desired product 3 as a light yellow oil. |
95% | With pyridine Ambient temperature; | |
75% | With perchloric acid for 0.5h; Ambient temperature; |
With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; platinum at 75℃; Hydrogenation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With boron trifluoride diethyl etherate In tetrahydrofuran for 7h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 1% 2: 75% | In tetrahydrofuran for 17h; Heating; | |
1: 7% 2: 58% | With tin(ll) chloride In 1,2-dimethoxyethane at 20℃; for 5h; Inert atmosphere; | Method B: To a suspension of lactone 2 (1.00 g, 6.75 mmol) in dry 1,2-dimethoxyethane(4 mL) were added benzaldehyde dimethyl acetal (1.32 mL, 8.79 mmol) and a catalyticamount of anhydrous SnCl2 (11 mg, 0.06 mmol). The reaction mixture was heated to refluxand stirred for 5 h under an argon atmosphere. After evaporation of the solvent under vacuum,the residue was purified by silica gel flash-column chromatography (hexane/AcOEt6:4 v:v) to afford compounds 11R (925 mg, 58% yield) and 11S (112 mg, 7% yield) as whitesolids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 1H-imidazole In N,N-dimethyl-formamide 1.) 65-70 deg C, 5 h, 2.) room temperature, overnight; | |
22% | With 1H-imidazole In N,N-dimethyl-formamide at 70℃; for 96h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen cation In acetone | |
90% | With boron trifluoride diethyl etherate In acetone at 20℃; for 1.5h; | |
86% | With boron trifluoride diethyl etherate In acetone at 20℃; Inert atmosphere; |
83% | With toluene-4-sulfonic acid In acetone at 0 - 20℃; for 2.08333h; | 2 2,3-isopropylidine-α-D-ribonolactone (2): Starting with commercially available α-D-ribonolactone (10.0 g, 67 mmol) and p-toluenesulfonic acid (200 mg) was dissolved in anhydrous acetone (150 ml) and cooled to 0-C. 2,2-Dimethoxy propane (7.55 g, 80.4 mmol) was added to the reaction slowly over a period of 5 minutes. The reaction was stirred for 2 hours at room temperature then sodium bicarbonate powder (250 mg) was added to the reaction, stirred for five minutes, filtered and concentrated. Column chromatography of the crude material gave 2,3-isopropylidine-α-D-ribonolactone(1.06 g, 82%). |
72% | With hydrogen cation In N,N-dimethyl-formamide at 26℃; for 12h; | |
72% | Stage #1: 2,2-dimethoxy-propane; D-Ribono-1,4-lactone at 60℃; for 4h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 20℃; for 0.166667h; | 1.1 D- (+)-RIBONOLACTONE (4.35g, 29.3 MMOL), 2,2-dimethoxypropane (18.1 ml, 146 mmol) and pyridinium p-toluene sulfonate (195 mg, 0.79 mmol) were mixed together. The light yellow mixture was heated at 60 C for 4 hours, and concentrated. The yellow oil was taken up in ethyl acetate, washed with saturated sodium bicarbonate and with brine. The organic layer. was dried with magnesium sulphate and concentrated to give a white solid, which was dissolved in THF and a solution of 0.1 M hydrochloric acid (10 ml) was added. The colourless mixture was stirred for 10 minutes at room temperature, concentrated to half volume, and diluted with ethyl acetate. The combined organic phases were washed with saturated sodium bicarbonate and brine, dried over magnesium sulphate and evaporated to give the desired product as a white solid, which was recrystallized from 1: 1 hexane: ethyl acetate, (3. 5G, 72%). MD=+70. 5 (C 1, CHC13) 'H NMR (CDC13, 300 MHz) 8 ppm: No. 1.40 (s, 3H, CH3), 1.50 (s, 3H, CH3), 2.60 (t, 1H, OH), 3.72 (dd, 1H, H-5), 4.71 (dd, 1H, H-5), 4.71 (t, 1H, H-3), 4.81 (d, 1H, H-4), 4.90 (d, 1H, H- 2). T3C NMR (CDC13, 300 MHz) 8 ppm: 25.10, 26.09, 62.18, 76.12, 78.30, 84.20, 113.98, 175.16. |
65% | Stage #1: 2,2-dimethoxy-propane; D-Ribono-1,4-lactone With pyridinium p-toluenesulfonate at 50℃; for 1h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 20℃; for 1h; | 7 To a stirred solution of D-(+)-ribonolactone (9.93 g, 67 mmol) in anhydrous 2,2-dimethoxypropane (40 mL) was added pyridinium p-toluene-4-sulfonate (PPTS) (0.37 g), and the reaction mixture was heated with stirring at 50° C. for 1 h. After evaporation of the solvent with rotary evaporator, the oily residue was dissolved in EtOAc (300 mL), then washed with saturated NaHCO3 (2×80 mL) and brine (2×80 mL), and dried (anhydrous Na2SO4). The solvent was evaporated with rotary evaporator, and the residue (14 g) was dissolved in THF (40 mL), and 1M HCl solution (10 mL) was added at room temperature. After being stirred at room temperature for 1 h, the reaction mixture was diluted with EtOAc (300 mL), then washed with saturated NaHCO3 (2×80 mL) and brine (2×80 mL), and dried (anhydrous Na2SO4). The solvent was evaporated in vacuo to dryness, and the crude products were purified recrystallized from hexane/EtOAc, affording 2,3-O-isoproylidene-D-ribonolactone (8.2g, 65% yield) as white crystal. |
63% | With toluene-4-sulfonic acid In methanol; acetone Ambient temperature; | |
With hydrogen cation In acetone | ||
With camphor-10-sulfonic acid In acetone | ||
19.0 g | With toluene-4-sulfonic acid; acetone for 12h; | |
With hydrogenchloride; pyridinium p-toluenesulfonate 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h; Yield given. Multistep reaction; | ||
With hydrogenchloride 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h; Yield given. Multistep reaction; | ||
With HCR-W2 H+-Dowex resin In acetone at 20℃; for 4h; | ||
With boron trifluoride diethyl etherate In acetone at 20℃; for 3h; Inert atmosphere; | To a suspension of crude D-ribonolactone (20 g) in acetone (120 mL) was added boron trifluoride etherate (1.71 mL, 13.5 mmol, 0.1 eq) followed by 2,2-dimethoxypropane (24 mL, 19.6 mmol, 1.3 eq) at room temperature and the reaction mixture was stirred for 3 hours. The resulting yellow suspension was filtered through a pad of Celite, the solids were washed with acetone (15 mL) and the filtrate was evaporated to dryness. The residue was dissolved in EtOAc (50 mL), extracted with H2O (40 mL) and brine (40 mL), respectively. The organic extract was dried over Na2SO4 and the solvent was removed under reduced pressure delivering protected D-ribonolactone (38, 12.4 g) in 66% yield over two steps as a light yellow oil, which was used without any further purification for the next step. | |
Stage #1: 2,2-dimethoxy-propane; D-Ribono-1,4-lactone With sulfuric acid In acetone at 20℃; for 0.833333h; Stage #2: With silver carbonate In acetone at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid | |
100% | With copper(II) sulfate at 20℃; for 48h; Inert atmosphere; | |
99% | With 4 A molecular sieve; sulfuric acid for 1.5h; Heating; |
98% | With copper(II) sulfate for 72h; Ambient temperature; | |
98% | With toluene-4-sulfonic acid for 16h; | 10 A mixture of (3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)dihydrofuran-2(3H)-one (40 g, 270 mmol) and p-toluenesulfonic acid monohydrate (500 mg, 2.63 mmol) was stirred in acetone (volume: 600 ml) for 16h. Then solid NaHCC (5g) was added, and the reaction mixture was stirred for lhour. The reaction mixture was filtered through celite and concentrated under reduced pressure to dryness. The product was triturated with hexanes, and the solid was collected by filtration and dried to give a 98% yield. |
95% | With hydrogen cation for 24h; Ambient temperature; | |
94% | With sulfuric acid for 6h; Ambient temperature; | |
93% | With sulfuric acid at 20℃; for 72h; | Synthesis of 2,3-O-isopropylidene-D-ribonic acid-1,4-lactone A solution of D-ribonic acid-l,4-lactone (270.0 g, 1.823 mol) and sulphuric acid (18.0 g, 0.182 mol, 0.1 equiv.) in acetone (2.79 L) was stirred at room temperature for 3 days. The reaction mixture was quenched by the addition of solid sodium bicarbonate (-450 g), filtered and the filtrate evaporated. The residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate; the combined organic layers were dried over magnesium sulphate, filtered and concentrated under reduced pressure to give the desired product as a white solid (318.8 g, 93%). 1H NMR (300 MHz, CDC13) δ 4.83 (d, J= 5.5 Hz, 1H), 4.77 (d, J= 5.5 Hz, 1H), 4.64-4.62 (m, 1H), 3.99 (ddd, J= 2.3, 5.5 and 12.4 Hz, 1H), 3.81 (ddd, J= 2.3, 5.5 and 12.4 Hz, 1H), 2.67 (t, J= 5.5 Hz, 1H), 1.46 (s, 3H), 1.37 (s, 3H). |
92% | With iodine for 12h; Ambient temperature; | |
91% | With sulfuric acid for 5h; | |
90% | With sulfuric acid at 0 - 20℃; for 5h; | |
89% | With sulfuric acid at 20℃; | |
86% | With sulfuric acid at 0 - 20℃; | |
85% | for 20h; Heating; | |
85% | With sulfuric acid for 5h; Ambient temperature; | |
85% | With sulfuric acid at 20℃; for 12h; | |
84% | With sulfuric acid | |
81% | With hydrogenchloride for 18h; Ambient temperature; | |
80% | With sulfuric acid at 20℃; for 12h; | |
80% | With sulfuric acid In acetone at 0 - 20℃; for 12h; | 3 The expoxide reagent may be synthesized as shown in Scheme 3. D-Ribonolactone 12 was converted to the 2,3-O-isopropylidene-D-ribonolactone 13; To a suspension of D-ribonolactone 12 (10 g, 68 mmol) in actone (200 mL) was added concentrated sulfuric acid (4 mL) dropwise while the solution was cooled in an ice bath. The starting material dissolved in 5 minutes. The mixture was stirred for 12 h at room temperature. Ammonia gas was passed through the ice-cooled solution. The resulting white solid was filtered off and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (Hexanes-EtOAc, 1:3) to afford 13 (10.6 g, 80%) as a white solid: mp 134-137° C.; lit. mp 135-138. |
79% | With hydrogenchloride at 26℃; for 18h; | |
75% | With hydrogenchloride In water at 20℃; for 18h; | |
62% | With hydrogenchloride for 4h; Ambient temperature; | |
48% | Stage #1: acetone; D-Ribono-1,4-lactone at 20℃; for 1h; Large scale; Stage #2: With sulfuric acid at 10℃; Large scale; | 1.2 Step 2: Preparation of 2,3-O-isopropylidene D-Ribono-1,4-lactone (19c) A 50-L jacketed reaction vessel was charged with D-ribono-1,4-lactone (19b) (3.0 kg, 20.27 mol), and 30 L of ACS grade acetone. The reaction mixture was stirred at roomtemperature for 1 h. The internal temperature of the reaction vessel was lowered to 10 ocand cone. sulfuric acid (49 mL) was added slowly to the reaction mixture. Upon addition of the sulfuric acid the internal reaction temperature was allowed to warm up slowly. Thereaction mixture was stirred at this temperature for 2.5- 3 h. The reaction was monitoredby TLC (TLC; 9:1, methylenechloride:methyl alcohol, R1= 0.75). The reaction mixturewas neutralized by addition of solid sodium bicarbonate ( ~500 g) until the pH was neutral. The reaction mixture was filtered over a funnel. The solid residue containing inorganicsalts was washed with acetone (3 L). The filtrate was transferred to a 20-L evaporationflask and evaporated to dryness (50 °C, 10 mmHg) to give a semi-solid compound. Theresidue was taken in ethyl acetate (3 L) and stirred at room temperature for 4 h on rotaryevaporator. The solid 2,3-0-isopropylidene D-Ribono-1,4-lactone (19c) was collected by filtration and dried in a vacuum oven for 16 hat 40 oc (0.1 mm Hg). Yield: 1.819 kg (48%); MP 136-140 oc; 1H NMR (CDCh) 8 4.8 (dd, 2 H), 4.6 (s, 1 H), 3.85 (dd, 2 H), 1.5 (s,3 H), 1.4 (s, 3 H). |
48% | With sulfuric acid at 10℃; Large scale; | 1.2 Step 2: Preparation of 2,3-O-isopropylidene D-Ribono- 1,4-lactone (lc) Step 2: Preparation of 2,3-O-isopropylidene D-Ribono- 1,4-lactone (lc) A 50-L jacketed reaction vessel was charged with D-ribono- 1,4-lactone (lb) (3.0 kg, 20.27 mol), and 30 L of ACS grade acetone. The reaction mixture was stirred at room temperature for 1 h. The internal temperature of the reaction vessel was lowered to 10 °C and cone, sulfuric acid (49 mL) was added slowly to the reaction mixture. Upon addition of the sulfuric acid the internal reaction temperature was allowed to warm up slowly. The reaction mixture was stirred at this temperature for 2.5 - 3 h. The reaction was monitored by TLC (TLC; 9: 1, methylenechloride: methyl alcohol, R/ = 0.75). The reaction mixture was neutralized by addition of solid sodium bicarbonate (-500 g) till the pH was neutral. The reaction mixture was filtered over a funnel. The solid residue containing inorganic salts was washed with acetone (3 L). The filtrate was transferred to a 20-L evaporation flask and evaporated to dryness (50 °C, 10 mm Hg) to give a semi-solid compound. The residue was taken in ethyl acetate (3 L) and stirred at room temperature for 4 h on rotary evaporator. The solid 2,3-O- isopropylidene D-Ribono-l,4-lactone (lc), was collected by filtration and dried in a vacuum oven for 16 h at 40 °C (0.1 mm Hg). Yield: 1.819 kg (48%); MP 136 -140 °C; 1H NMR (CDCls) δ 4.8 (dd, 2 H), 4.6 (s, 1 H), 3.85 (dd, 2 H), 1.5 (s, 3 H), 1.4 (s, 3 H). |
42% | With hydrogenchloride at 25℃; for 0.25h; | Preparation of 2,3-O-isopropylidene-D-ribonolactone (5)3,4,7 D-Ribonolactone 2 (148 mg, 1.0 mmol) and acetone (1.5 mL) were added into a 10 mL round-bottomed flask with a magnetic stirring bar and then 0.1 mL (2 drops) of 12 mol L-1 HCl was added at 25 °C. After 15 min, 0.5 mLof CH2Cl2 was poured to dissolve the white solid formed during the course of the reaction. Then the white mixture was quenched by pouring 300 mg of powdered NaHCO3 in small portions (5 min, until CO2 effervescence ceases), which turned the mixture into a yellow color. The liquid phase was decanted and a second portion of CH2Cl2 (0.5 mL) was added to the reaction residue to extract additional white solid. This process was repeated a second time and the combined CH2Cl2 extracts were evaporated to dryness using a rotary evaporator to give 5 as a colorless solid (80 mg, 42% yield). |
With hydrogen cation | ||
With sulfuric acid | ||
With sulfuric acid for 5h; Ambient temperature; | ||
With sulfuric acid at 20℃; for 30h; | 1,4-Anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol (3)21,23 To asolution of S1 in acetone (500 mL) was added conc. H2SO4 (2.5 mL), and the reaction mixture was stirred for 30 h at room temperature. After being cooled to 0 °C, the reaction mixture was neutralized with sodium bicarbonate. The resulting solids were filtered through a Celite pad, and washed with hot acetone. The combined filtrate and washings were concentrated in vacuo, and partitioned between CHCl3 and H2O, the organic layer was washed with brine, dried (Na2SO4) and concentratedin vacuo to give crude S2 (45.32 g). | |
With sulfuric acid at 20 - 30℃; for 12h; Inert atmosphere; | The brown solid was dissolved in 500 L of acetone (1185 kg, 20403 mol, 41 equiiv) and 7.5 L of sulfuric acid (Sulfuric acid) was heated to a boiling point under nitrogen condition for 4 hours. Thereafter, the reaction mixture was cooled to 20-30 ° C. and kept at temperature for 8 hours. the pH of the reaction mixture was adjusted to 5.5-6.0 using sodium hydroxide, filtered, and titrated in a vacuum at 40 ° C. to obtain a solid product. the crude solid product was dissolved by stirring at 250 ° C. with 250 L of ethyl acetate, then the solution was filtered and titrated in vacuo by 50% of the initial volume. the solution was then cooled to -5 ° C to give solid compound 9, which was purified by filtration and drying in 35 ° C vacuum. | |
With sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In N,N-dimethyl-formamide at 20℃; for 1h; | |
93% | In methanol | 1 Example 1 Example 1 (No Heteroatom) Preparation of Dodecyl D-Ribonamide (Used for Comparative Purposes) A 200 ml four necked round bottom flask equipped with a condenser, addition funnel, thermometer and mechanical stirrer was charged with D-ribono-1,4-lactone (15.0 g, 0.10 mole) and methanol (45 g, for 43% total solids). The suspension was heated to 40°-43° C. for 15 minutes and the heating mantle removed. Dodecylamine (18.8 g, 0.10 mole) containing methanol (5 ml) was added dropwise over 1/2 hour. The reaction mixture was allowed to cool to room temperature (about 21° C.) followed by stirring overnight to allow complete crystallization. The white product was filtered, washed with methanol (3*20 ml) and dried under vacuum at 40°-45° C. giving 31.5 g (93% yield) of dodecyl D-ribonamide with a melting point of 101°-102° C. and 99.9% purity. |
93% | In methanol | 1 Example 1 Example 1 (No Heteroatom) Preparation Of Dodecyl D-Ribonamide (Used for Comparative Purposes) A 200 ml four necked round bottom flask equipped with a condenser, addition funnel, thermometer and mechanical stirrer was charged with D-ribono-1,4-lactone (15.0 g, 0.10 mole) and methanol (45 g, for 43% total solids). The suspension was heated to 40°-43° C. for 15 minutes and the heating mantle removed. Dodecylamine (18.8 g, 0.10 mole) containing methanol (5 ml) was added dropwise over 1/2 hour. The reaction mixture was allowed to cool to room temperature (about 21° C.) followed by stirring overnight to allow complete crystallization. The white product was filtered, washed with methanol (3*20 ml) and dried under vacuum at 40°-45° C. giving 31.5 g (93% yield) of dodecyl D-ribonamide with a melting point of 101°-102° C. and 99.9% purity. |
93% | In methanol | 1 Example 1 Example 1 (No Heteroatom) Preparation of Dodecyl D-Ribonamide (Used for Comparative Purposes) A 200 ml four necked round bottom flask equipped with a condenser, addition funnel, thermometer and mechanical stirrer was charged with D-ribono-1,4-lactone (15.0 g, 0.10 mole) and methanol (45 g, for 43% total solids). The suspension was heated to 40°-43° C. for 15 minutes and the heating mantle removed. Dodecylamine (18.8 g, 0.10 mole) containing methanol (5 ml) was added dropwise over 1/2 hour. The reaction mixture was allowed to cool to room temperature (about 21° C.) followed by stirring overnight to allow complete crystallization. The white product was filtered, washed with methanol (3*20 ml) and dried under vacuum at 40°-45° C. giving 31.5 g (93% yield) of dodecyl D-ribonamide with a melting point of 101°-102° C. and 99.9% purity. |
93% | In methanol | 1 Preparation of Dodecyl D-Ribonamide Preparation of Dodecyl D-Ribonamide A 200 ml four necked round bottom flask equipped with a condenser, addition funnel, thermometer and mechanical stirrer was charged with D-ribono-1,4-lactone (15.0 g, 0.10 mole) and methanol (45 g, for 43% total solids). The suspension was heated to 40°-43° C. for 15 minutes and the heating mantle removed. Dodecylamine (18.8 g, 0.10 mole) containing methanol (5 ml) was added dropwise over 1/2 hour. The reaction mixture was allowed to cool to room temperature (about 21° C.) followed by stirring overnight to allow complete crystallization. The white product was filtered, washed with methanol (3*20 ml) and dried under vacuum at 40°-45° C. giving 31.5 g (93% yield) of dodecyl D-ribonamide with a melting point of 101°-102° C. and 99.9% purity. |
In methanol at 20℃; for 4h; | ||
In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridinium p-toluenesulfonate In dichloromethane for 3h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridinium p-toluenesulfonate In dichloromethane for 0.5h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With Sikkon; iron(III) chloride at 50℃; for 2.5h; | |
60% | With anhydrous calcium sulphate; iron(III) chloride at 50℃; for 3h; | |
60% | With copper(II) sulphate In dichloromethane at 40 - 45℃; for 48h; Inert atmosphere; | 1 EXAMPLE 1 : Preparation of the compound of formula 2a To a round bottom flask was added 1 (500 g, 1.0 eq), copper sulphate (1616 g, 3.0 eq), cyclohexanone (663 g, 2 eq) and dichloromethane (5 L, 10 parts v/w). The mixture was agitated at 40-45°C for 48 h under nitrogen. 1H NMR. (CD3OD) analysis indicated reaction completion. The reaction mixture was cooled to 20-24°C and the insoluble material was removed by filtration and rinsed with dichloromethane (1 L, 2 parts v/w). The filtrate was washed with 50% saturated NaCI (2 L, 4 parts v/w) solution (2 L, 4 parts v/w) and then concentrated to 3 parts v/w under reduced pressure. Heptane (2 L, 4 parts v/w) was charged slowly over 30 min at 20-24°C and the resulting slurry was agitated for 16 h at this temperature. The mixture was filtered, washed with heptane (2 x IL, 2 x 2 parts v/w), and dried under vacuum under nitrogen to give 2a (466 g) as a white solid in 60% yield. 1H NMR. (300 MHz, Chloroform-d) 5 4.89 - 4.75 (m, 2H), 4.66 (t, J = 2.1 Hz, 1H), 4.01 (ddd, J = 12.2, 5.4, 2.3 Hz, 1H), 3.82 (ddd, J = 12.3, 5.7, 1.8 Hz, 1H), 2.62 (d, J = 6.2 Hz, 1H), 1.80 - 1.29 (m, 13H). |
56% | With sulfuric acid at 25℃; for 20h; | |
13 kg | With toluene-4-sulfonic acid at 70℃; for 12h; Large scale; | 2 Synthesis of compound C: Add p-toluenesulfonic acid (catalytic amount) and cyclohexanone (40L) to the above reaction solution, and the temperature is raised to 70° C. to react for 12 hours. HPLC detects that the raw material has reacted completely.Concentrate to dryness, add ethyl acetate, wash with sodium bicarbonate, and then wash with saturated sodium chloride. Concentrate and dry the organic phase to obtain the product compound C (13kg). The yield of the two steps is 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In pyridine at 60 - 65℃; | |
88% | With pyridine; dmap at 20 - 70℃; for 16h; | |
88% | With pyridine; dmap at 70℃; | 2 5-0-trityl-D-ribono-l, 4-lactone (SI): Synthesized with modification of previous report (J. Org. Chem. 2002, 67, 4466). Specifically, to a 250 mL round bottom flask was added D-ribonic acid g-lactone (2.15 g, 14.5 mmol, 1 eq), 4-dimethylaminopyridine (360 mg, 2.9 mmol, 0.2 eq), and pyridine (42 mL). Once fully dissolved, triphenylmethyl chloride (4.86 g, 17.4 mmol, 1.2 eq) was added as a solid in one portion to the stirring reaction mixture at room temperature. The solution was stirred at 70°C for 16 h. The cooled reaction mixture was diluted with dichloromethane and washed with 1 M HC1 twice and satd aq NaHC03 once. The organic layer was dried over MgS04, filtered through a pad of celite, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with 1 : 1 hexanes-EtOAc, yielding compound SI as a white solid (5.0 g, 88%). 3H NMR (500 MHz, DMSO-i) d 7.41 - 7.24 (m, 15H), 5.93 (d, J = 7.6 Hz, 1H), 5.45 (d, J = 4.0 Hz, 1H), 4.54 (dd, J = 7.6, 5.5 Hz, 1H), 4.39 - 4.34 (m, 1H), 4.02 (ddd, J = 5.3, 4.0, 1.2 Hz, 1H), 3.41 - 3.33 (m, 1H), 3.14 (dd, J = 11.0, 3.8 Hz, 1H). 13C NMR (126 MHz, DMSO-i) d 176.2, 143.2, 128.2, 128.1, 127.3, 86.7, 83.4, 69.4, 68.6, 63.0. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for CiiHiiOsNa 413.1365; Found 413.1362. |
84% | In pyridine at 70℃; for 16h; | |
83% | With pyridine; dmap at 80℃; | |
81% | With pyridine; dmap at 45℃; for 12h; | |
67% | With pyridine at 55℃; for 16h; | |
61% | In pyridine Ambient temperature; 1 h, then 2 days; | |
61% | With pyridine; dmap at 70℃; for 16h; | |
With pyridine at 65℃; for 20h; | ||
With pyridine at 70℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 2,6-dimethylpyridine; silver nitrate In N,N-dimethyl-formamide for 0.333333h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogenchloride for 7h; Ambient temperature; | |
89% | With hydrogenchloride | |
89% | With hydrogenchloride |
81% | With hydrogenchloride at 20℃; | 3.4. 3,4-O-(R)-Benzylidene-D-Ribono-1,5 Lactone (12R) To a solution of D-(+)-ribono-1,4-lactone 2 (1.00 g, 6.75 mmol) in benzaldehyde (9 mL),concentrated hydrochloric acid (0.9 mL) was added and the mixture was stirred at roomtemperature. After 20 minutes, the formation of a precipitate begins, and it increases duringthe time. The reaction was stirred at room temperature overnight, and then, Et2O (20 mL)was added to the semi-solid heterogeneous reaction mixture. A white solid was collectedby filtration, and it was washed with 10% aqueous sodium bicarbonate (10 mL) and water(10 mL). Finally, the product was refluxed for 20 minutes in acetone (100 mL), then themixture was left to cool at room temperature and the solid was filtered, yielding 12R as apure white solid (1.29 g, 81% yield), TLC (hexane/AcOEt; 3:7 v:v) Rf 0.25; mp 232-234 C[lit. [30] 230-231.5 C]; []25D 173 (c 1.0, DMF) [lit. [30] 180.5 (c 0.47, DMF)]. |
63% | With hydrogenchloride for 20h; Ambient temperature; | |
63% | With hydrogenchloride for 20h; Ambient temperature; | |
50% | Stage #1: benzaldehyde; D-Ribono-1,4-lactone at 50℃; for 0.166667h; Stage #2: With hydrogenchloride at 90℃; for 1.5h; | Preparation of 3,4-O-benzylidene-D-ribonolactone (6)7 Benzaldehyde (0.58 mL, 0.57 mmol) was added into a 25 mL round-bottomed flask followed by D-ribonolactone 2 (85 mg, 0.57 mmol). The temperature was raised to 50 °C for 10 min until a milky mixture was formed. Then, 0.05 mL (1 drop) of 12 mol L-1 HCl was added and the mixture was left reacting at 90 °C for 1.5 h .After cooling down to 25 °C, 7 mL of Et2O was added over the pinkish/yellowish crude mixture and the insoluble solid was separated by filtration and washed with 3 mL of 5% NaHCO3, 3 mL of H2O, and 3 mL of Et2O to give 6 as a white solid (94 mg, 50% yield). |
With hydrogenchloride | ||
With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With pyridine In chloroform | |
91% | With pyridine In chloroform for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In N,N-dimethyl-formamide at 20℃; for 1h; | |
In methanol at 20℃; for 15h; | ||
In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With pyridine In acetone at 0℃; for 5h; | 2 Typical procedure for the synthesis of 2,5-ditosyloxy-2,5-dideoxy- and 2,6-ditosyloxy-2,6-dideoxy-d-glycono-1,4-lactones General procedure: To a solution of aldono-1,4-lactone (3.0g, 0.02mol) in dry pyridine (15mL) at 0°C was added TsCl (8.88g, 0.047mol) dissolved in acetone (15mL) over a period of 10min. The reaction mixture was then stirred at 0°C for a given period of time after which it was neutralized with 6M HCl until pH 1. The compound was extracted using EtOAc (3×15mL), dried (Na2SO4), and concentrated and subjected to column chromatography (elution with EtOAc:hexanes) to give the pure ditosylaldono lactone. 1.2.2 2,5-Di-O-tosyl-ribono lactone (7) IR (neat): 3438, 1777, 1424, 1219, 1181, 1073, 1028, 993 cm-1; 1H NMR (400 MHz, CD3COCD3) δ 2.44 (s, 6H), 4.34-4.49 (m, 2H), 4.66 (t, J = 3.4 Hz, 1H), 5.23 (d, J = 5.2 Hz, 1H), 5.38 (t, J = 4.4 Hz, 1H), 7.48 (d, J = 7.9 Hz, 4H), 7.77 (d, J = 8.3 Hz, 2H), 7.84 (d, J = 8.3 Hz, 2H) ppm; 13C NMR (100 MHz, CD3COCD3) δ 20.6, 20.7, 68.17, 68.3, 73.8, 82.7, 127.8, 128.1, 130.0, 130.2, 132.3, 132.7, 145.6, 145.7, 168.7 ppm; HRMS for C19H20O9S2Na [M+Na]+ calcd 479.0446; found 479.0443. |
45% | With pyridine In acetone at 0℃; for 5h; | |
45% | With pyridine In acetone at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With toluene-4-sulfonic acid for 48h; Ambient temperature; | |
82% | With toluene-4-sulfonic acid In methanol; acetone for 48h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 1H-imidazole In N,N-dimethyl-formamide Ambient temperature; | |
76% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 18h; Cooling with ice; | |
70% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 1h; |
70% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 1h; | |
With 1H-imidazole In N,N-dimethyl-formamide at -20 - -15℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With rhodium hydrido (PEt3)3 complex; 1-Phenylbut-1-en-3-one In N,N-dimethyl-formamide at 40℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sulfurous dibromide In N,N-dimethyl-formamide at 20℃; for 0.5h; | |
95% | With sulfurous dibromide In N,N-dimethyl-formamide | |
95% | With sulfurous dibromide In N,N-dimethyl-formamide |
55% | With pyridine; carbon tetrabromide; triphenylphosphine for 2h; Ambient temperature; | |
With sulfurous dibromide In N,N-dimethyl-formamide at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: D-Ribose With bromine; sodium hydrogencarbonate In water; acetone at 0℃; for 1.83333h; Stage #2: With sodium hydrogensulfite In water; acetone at 0℃; | |
65% | Stage #1: D-Ribose With sodium hydrogencarbonate In water at 20℃; for 1h; Large scale; Stage #2: With bromine at 5 - 10℃; for 5.5h; Large scale; | 1.1 Step 1: Preparation of D-Ribono lactone ( 19b) A 22-L three-neck flask fitted with a mechanical stirrer, a 1L pressure-equalizingaddition funnel, and an efficient condenser was charged with D-ribose (19a) (2.0 kg, 13.33mol) solid sodium bicarbonate (2.24 kg, 26.66 mole) and water (12 L). The reactionmixture was stirred at room temperature for 1 h at which time most of the solid disappeared. The reaction vessel was placed in an ice bath with the internal temperature maintained at 5 ± 1 °C. The addition funnel was filled with bromine (710 mL, 13.86 mol)and the bromine was added to the vigorously stirred aqueous solution at a rate of about 5mL/min such that the temperature was maintained between 5-10 °C. When the additionwas completed (about 2.5 h) the resulting orange solution was stirred for an additional 3 h. To the reaction mixture was added solid sodium hydrogen sulfite ( ~ 75 g) in small lots untilthe orange color was completely discharged. The clear aqueous solution was transferred toa 20-L evaporating flask, and evaporated to dryness on a rotary evaporator (80 °C, 10 mmHg) over a period of 4 h, to leave a semi-solid residue. To the residue was added ethylalcohol ( ~ 4 L) and stirred at 40 oc for 1 h. The mixture was cooled down and filtered over a funnel to remove most of the insoluble inorganic salts. The solid residue was washedwith ethyl alcohol (1 L). The filtrate was transferred to a 20-L evaporating flask andconcentrated to dryness on a rotary evaporator (50 °C, 10 mm Hg) to furnish a solidresidue. To this residue was added ethyl alcohol(~ 3 L) and the slurry was stirred at roomtemperature for 12 h. The solid was collected by filtration and washed with ethyl alcohol25 (750 mL). The product D-Ribono lactone (19b) was dried in a vacuum oven at 40 oc (0.1mmHg). Yield 1.28 kg (65 %); M.P. 77- 80 oc; 1H NMR (D20) 8 4.72 (d, 1 H), 4.57 (t, 1H), 4.42 (d, 1 H), 3.80 (m, 2 H). |
65% | Stage #1: D-Ribose With water; sodium hydrogencarbonate at 20℃; for 1h; Large scale; Stage #2: With bromine In water at 5 - 10℃; for 5.5h; Large scale; | 1.1 Step 1 : Preparation of D-Ribono lactone (lb) Step 1 : Preparation of D-Ribono lactone (lb) A 22-L three-neck flask fitted with a mechanical stirrer, a 1 L pressure-equalizing addition funnel, and an efficient condenser was charged with D-ribose (la) (2.0 kg, 13.33 mol) solid sodium bicarbonate (2.24 kg, 26.66 mole) and water (12 L). The reaction mixture was stirred at room temperature for 1 h at which time most of the solid disappeared. The reaction vessel was placed in an ice-bath with the internal temperature maintained at 5 ± 1 °C. The addition funnel was filled with bromine (710 mL, 13.86 mol) and the bromine was added to the vigorously stirred aqueous solution at a rate of about 5 mL/min such that the temperature was maintained between 5-10 °C. When the addition was completed (about 2.5 h) the resulting orange solution was stirred for an additional 3 h. To the reaction mixture was added solid sodium hydrogen sulfite (~ 75 g) in small lots until the orange color was completely discharged. The clear aqueous solution was transferred to a 20-L evaporating flask, and evaporated to dryness on a rotary evaporator (80 °C, 10 mm Hg) over a period of 4 h, to leave a semi-solid residue. To the residue was added ethyl alcohol (~ 4 L) and stirred at 40 °C for 1 h. The mixture was cooled down and filtered over a funnel to remove most of the insoluble inorganic salts. The solid residue was washed with ethyl alcohol (1 L). The filtrate was transferred to a 20-L evaporating flask and concentrated to dryness on a rotary evaporator (50 °C, 10 mm Hg) to furnish a solid residue. To this residue was added ethyl alcohol (~ 3 L) and the slurry was stirred at room temperature for 12 h. The solid was collected by filtration and washed with ethyl alcohol (750 mL). The product D-Ribono lactone (lb) was dried in a vacuum oven at 40 °C (0.1 mm Hg). Yield 1.28 kg (65%); M.P. 77 - 80 °C; 1H NMR (D20) δ 4.72 (d, 1 H), 4.57 (t, 1 H), 4.42 (d, 1 H), 3.80 (m, 2 H). |
With phosphate buffer; [Ru(2,2':6':2''-terpyridine)(2,2'-bipyridine)O](2+) at 25℃; ΔH(excit.), ΔS(excit.); | ||
With bromine; potassium carbonate In water at 10 - 20℃; Large scale; | ||
With bromine; sodium hydrogencarbonate In water at 0 - 5℃; | A vigorously stirred solution of D-ribose (15 g, 100 mmol, 1.0 eq) and NaHCO3 (16.8 g, 200 mmol, 2.0 eq) in H2O (90 mL) was cooled to 0 °C and bromine (5.4 mL, 104 mmol, 1.04 eq) was added slowly (20 min) via an additional funnel. During the addition the temperature of the reaction mixture was controlled by an internal thermometer and did not exceed 5 °C. When the addition was completed the orange solution was stirred for an additional hour. Solid NaHSO3 (1.26 g, 10 mmol, 0.1 eq) was added to destroy the excess of bromine. The water in the colorless reaction mixture was removed on a rotary evaporator (bath temperature 60 °C) until a yellow wet slurry remained. Afterwards EtOH (60 mL) and toluene (30 mL) were added to give a cloudy suspension and the solvent was removed under reduced pressure to give a damp solid. Again EtOH (60 mL) was added and the crude product mixture was heated to reflux on an oil bath for 30 minutes. The hot ethanolic suspension was filtered and the solids were rinsed once with hot EtOH (15 mL). The filtrate was cooled and stored in the refrigerator for 16 hours. The crystalline product was filtered, washed first with cold EtOH (10 mL), then with Et2O (10 mL) and dried under vacuum to yield 20 g of crude product (the major contaminant is NaBr) The crude material was used without any further purification for the acetonide protection. | |
Stage #1: D-Ribose With sodium hydrogencarbonate In water at 20℃; for 0.25h; Stage #2: With bromine In water | Three-step preparation of 2,3-di-O-acetyl-D-ribonolactone (4) D-ribose (1, 10.0 g, 67.0 mmol), sodium bicarbonate (11.2 g, 130 mmol), and water (60 mL) were added in a 125 mL three-necked round-bottomed flask with an internal thermometer, a pressure-equalizing addition funnel and stirring bar. The mixture was stirred at room temperature for 15 min. Then, the flask was immersed in an ice-water bath. Bromine (1.12 g, 70 mmol) was added to the vigorously stirred aqueous solution through the addition funnel at a rate such that the reaction temperature was kept under 5 °C. After the addition, the funnel was replaced with a stopper and the mixture stirred for another 50 min. Sodium bisulfite (0.65 g, 6.25 mmol) was added and the orange color solution turned transparent. Then, the aqueous solution was transferred to a 250 mL flask and evaporated on a rotary evaporator to give a wet slurry. Absolute EtOH (40 mL) and toluene (10 mL) were added to the cloudy suspension and the solvent removed by rotary evaporation to provide a damp solid. Absolute EtOH (40 mL) was poured to the crude and the mixture heated on a steam bath for 30 min. The hot ethanolic suspension was filtered and the solids rinsed with hot absolute EtOH (10 mL). After refrigerating overnight, white crystals were formed, filtered, rinsed with cold absolute EtOH (10 mL) followed by Et2O (10 mL) to give, after drying under vacuum, 8.16 g of a white solid (it is expected 35-45% of NaBr).3 Part of D-ribonolactone from the previous procedure (2.20 g), 13X/KCl molecular sieves (3.0 g) and Ac2O (20 mL) were stirred at 25 °C for 3 h. The reaction was quenched with EtOAc (20 mL) and filtered through a short pad of Celite. The solvent was azeotropically removed using toluene (2 × 5 mL) asco-solvent in rotary evaporator to give 1.46 g of the crude acylated product 3 (> 95% pure by 1H NMR) that was used in the next step without further purification. To a mixture of 2,3,5-tri-O-acetyl-D-ribonolactone (3, 1.46 g, 4.80 mmol) in EtOH (50 mL) was added CAL-B (730 mg) and the reaction was left in a temperature-controlled incubator shaker (180 rpm, 35 °C) for 6 h. Next, the supernatant solution was decanted and the enzyme washed with MeOH (10 mL) followed by ACN (10 mL). The combined solvents were removed under reduced pressure to give a light yellow oil after purification by flash column chromatography using1:1 EtOAc/hexanes to give 570 mg of 2,3-di-O-acetyl-D-ribonolactone(4). Overall yield 14% from 1. | |
With bromine; potassium carbonate In water at 0℃; for 1.5h; | 1,4-Anhydro-5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-D-ribitol (3)21,23 To a solution of D-Ribose (45.0 g, 0.30 mol) in H2O (300 mL) containing K2CO3 (49.76 g, 0.36 mol) was added Br2 (17 mL, 0.33 mol) dropwisely at 0 °C. After being stirred for 1.5 h, the reaction was quenched by addition of sat. aqueous NaHCO3 and concentrated in vacuo to give crude S1. | |
80 g | Stage #1: D-Ribose With sodium hydrogencarbonate In water at 20℃; for 0.25h; Stage #2: With bromine In water at 5℃; for 1.83333h; | |
19.7 g | Stage #1: D-Ribose With sodium hydrogencarbonate In water for 0.583333h; Inert atmosphere; Stage #2: With bromine In water at 0 - 20℃; for 72h; Inert atmosphere; | |
With bromine; potassium carbonate In water at 0 - 20℃; | 750 kg (500 mol, 1.0 equiv) of D-ribose after dissolving in 207 L of water at room temperature, it was cooled to 10 - 15 °C and 82.5 kg (597 mol, 1.2 equiiv) of solid potassium carbonate was added, the temperature was kept at 10-15 °C. After the reaction solution was cooled to 0-5 ° C., 87.4 kg (547 mol, 1.1 equiiv) of bromin was added, followed by stirring for 3-4 hours. After the bromine addition was complete, the reaction mixture was stirred at rt overnight. thereafter, 88% formic acid (25 L) was added thereto to adjust the pH to 2-3, and the acid solution was titrated at 505 °C under vacuum to obtain a brown solid. | |
With bromine; potassium carbonate In water | ||
With bromine; sodium hydrogencarbonate In water at 20℃; for 1h; | 1 Synthesis of compound B: Add water (45L), D-ribose (9kg, 60mol) and sodium bicarbonate (12.6kg, 150mol) to a 100L reactor connected with an exhaust gas absorption device, and add bromine (19.2kg, 120mol) dropwise at 20°C, After dripping, react at 20°C for 1 hour, and HPLC detects that the reaction of the raw materials is complete.Cool down to 0°C and add sodium sulfite to quench the reaction, and then proceed to the next step. | |
Stage #1: D-Ribose With sodium hydrogencarbonate In water at 20℃; for 0.25h; Stage #2: With bromine In water at 5 - 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; | |
51% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 0.25h; Inert atmosphere; Molecular sieve; | |
39% | In pyridine for 5h; Ambient temperature; |
33% | With 1H-imidazole In N,N-dimethyl-formamide at 0℃; Inert atmosphere; | Synthesis of TIPDS-protected lactone 6: (γ)-Ribonolacton (5, 1.17 g, 7.90 mmol, 1.00 equiv), imidazole (2.61 g, 38.3 mmol, 4.85 equiv) and molecular sieves (4 Å, 1.00 g) were dispersed in dry DMF (80.0 mL). The suspension was cooled to 0 °C. 1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane (3.0 mL, 2.90 g, 9.13 mmol, 1.15 equiv) was added dropwise and the reaction mixture was stirred for further 5 min at 0 °C. After the addition of an aqueous NH4Cl solution (50 mL) and warming to room temperature, the layers were separated. The aqueous layer was extracted with EtOAc (3 × 100 mL). The combined organic layer was washed with water (5 × 150 mL), brine (150 mL), dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash column chromatography (PE/EtOAc 9:1) delivering the TIPDSi-protected lactone 6 (1.01 g, 2.59 mmol, 33%) as colorless oil. Rf (PE:EtOAc = 2:1) = 0.88; [α]D20 = +17.7 (c = 1.0, CHCl3); S. Hildbrand, A. Blaser, S. P. Parel, C. J. Leumann, J. Am. Chem. Soc. 1997, 119, 5499-5511: [α]D20 = +28.9, c = 0.5, CHCl3; 1H NMR (400 MHz, CDCl3): δ [ppm] = 4.49 (dd, J = 6.9, 5.8 Hz, 1 H), 4.43 (ddd, J = 6.9, 5.8, 3.5 Hz, 1 H), 4.23 (d, J = 5.8 Hz, 1 H), 4.13 (dd, J = 12.6, 3.5 Hz, 1 H), 3.99 (dd, J = 12.6, 5.8 Hz, 1 H), 3.16 (bs, 1 H), 1.09-1.03 (m, 24 H), 0.97-0.81 (m, 4 H); 13C NMR (100 MHz, CDCl3): δ [ppm] = 172.2, 82.2, 69.9, 68.8, 61.6, 17.5, 17.4, 17.3, 17.3, 17.2, 17.0, 17.0, 16.9, 13.4, 13.2, 12.9, 12.7; HRMS (ESI): calc. for C17H34O6Si2Na [M+Na]+: 413.1786, found: 413.1782. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With trifluorormethanesulfonic acid In 1,4-dioxane at 0℃; for 3h; Inert atmosphere; | |
70% | With trifluorormethanesulfonic acid In 1,4-dioxane pH 3; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With thionyl chloride In N,N-dimethyl-formamide at 20℃; | |
95% | With sulfuryl dichloride In N,N-dimethyl-formamide at 20℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydroxylamine at 20℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With pyridinium p-toluenesulfonate; sodium sulfate at 60℃; for 1h; | |
94% | With pyridinium p-toluenesulfonate; sodium sulfate | |
84% | With pyridinium p-toluenesulfonate; sodium sulfate at 60℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With water at 80℃; for 0.25h; microwave irradiation; | |
99 % Chromat. | With erbium(III) triflate In water at 120℃; for 0.0833333h; Microwave irradiation; | |
Multi-step reaction with 3 steps 1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 6 h / 20 °C / Cooling with ice 2: ethanol / 6 h / 70 °C 3: palladium on activated charcoal; hydrogen / ethanol / 6 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: pyridine / 70 °C 2: imidazole / dimethylformamide / 48 h / 20 °C 3: 93 percent / LiBH4 / tetrahydrofuran 4: 84 percent / pyridine; DMAP 5: 76 percent / 60 h / 80 °C 6: H2 / Pd/C / ethanol 7: Et3N / ethanol; toluene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: pyridine / 70 °C 2: imidazole / dimethylformamide / 48 h / 20 °C 3: 93 percent / LiBH4 / tetrahydrofuran 4: 84 percent / pyridine; DMAP 5: 76 percent / 60 h / 80 °C 6: H2 / Pd/C / ethanol 7: Et3N / ethanol; toluene 8: 57 percent / HCOOH / acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: pyridine / 70 °C 2: imidazole / dimethylformamide / 48 h / 20 °C 3: 93 percent / LiBH4 / tetrahydrofuran 4: 84 percent / pyridine; DMAP 5: 76 percent / 60 h / 80 °C 6: H2 / Pd/C / ethanol 7: Et3N / ethanol; toluene 8: 57 percent / HCOOH / acetonitrile 9: 55 percent / RuCl3*xH2O; NaIO4 / acetonitrile; CCl4; H2O |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: pyridine / 70 °C 2: imidazole / dimethylformamide / 48 h / 20 °C 3: 93 percent / LiBH4 / tetrahydrofuran 4: 84 percent / pyridine; DMAP 5: 76 percent / 60 h / 80 °C 6: H2 / Pd/C / ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / 70 °C 2: imidazole / dimethylformamide / 48 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 83 percent / pyridine; DMAP / 80 °C 2: 97 percent / imidazole / dimethylformamide / 48 h / 20 °C | ||
Multi-step reaction with 2 steps 1: dmap; pyridine / 16 h / 70 °C 2: 2,6-dimethylpyridine / dichloromethane / 1.5 h / 0 °C |
Multi-step reaction with 2 steps 1: dmap; pyridine / 16 h / 20 - 70 °C 2: 1H-imidazole / N,N-dimethyl-formamide / 16 h / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1: dmap; pyridine / 70 °C 2: 1H-imidazole / N,N-dimethyl-formamide / 16 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 67 percent / pyridine / 16 h / 55 °C 2: 85 percent / pyridine / CH2Cl2 / 2 h / -78 - -15 °C | ||
Multi-step reaction with 2 steps 1: pyridine / 20 h / 65 °C 2: pyridine / CH2Cl2 / 3 h / -78 - 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 67 percent / pyridine / 16 h / 55 °C 2: 85 percent / pyridine / CH2Cl2 / 2 h / -78 - -15 °C 3: 87 percent / Ph3As; LiCl / [Pd2(dba)3] / tetrahydrofuran / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 98 percent / aq. HCl / 7 h / Ambient temperature 2: 1.) NaH 3: 93 percent / n-Bu3SnH, AIBN / toluene / Heating 4: 96 percent / TFA / H2O; CHCl3 / 10 h / 70 °C 5: 84 percent / pyridine / 4 h / Ambient temperature 6: 1.) PPh3, DEAD, 2.) MeI / 1.) benzene, rt, 24 h, 2.) toluene, rt, 30 min, reflux, 24 h 7: 60 percent / H2 / Pd/C / ethanol / 12 h / Ambient temperature 8: 77 percent / p-TsOH / methanol / 5 h / Ambient temperature | ||
Multi-step reaction with 3 steps 1: 1.) THF, 12 h, reflux, 2.) 7 d 2: 68 percent / 220 °C / 40 Torr 3: H2 / 10 percent Pd/C / ethyl acetate / 760 Torr | ||
Multi-step reaction with 3 steps 1: imidazole / dimethylformamide / 1 h / -20 - -15 °C 2: tetrahydrofuran / 0.25 h / Ambient temperature 3: Raney nickel / tetrahydrofuran / 4 h / Heating |
31 %Spectr. | With palladium 10% on activated carbon; hydrogen; tetrabutylammonium perrhenate In ethanol at 70℃; for 8h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 98 percent / aq. HCl / 7 h / Ambient temperature 2: 1.) NaH 3: 93 percent / n-Bu3SnH, AIBN / toluene / Heating 4: 96 percent / TFA / H2O; CHCl3 / 10 h / 70 °C | ||
Multi-step reaction with 4 steps 1: conc. HCl 2: NaH / dimethylformamide 3: n-Bu3SnH, AIBN / toluene / Heating 4: aq. CF3CO2H / CHCl3 / Heating | ||
Multi-step reaction with 2 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: hydrogen, triethyl amine / Pd/C / ethyl acetate |
Multi-step reaction with 4 steps 1: 92.7 percent / hydrochloric acid / 7 h 2: 1.) sodium hydride / 1.) DMF, sodium hydride 3: 92.5 percent / tri-n-butyltin hydride / toluene / Heating 4: CHCl3; trifluoroacetic acid; H2O / 10 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 2.1: sodium hydride 3.1: polymethylhydrosiloxane / titanocene di-p-chlorophenoxide; tetrabutylammonium fluoride on alumina / toluene / 20 °C 3.2: 95 percent / aq. NaOH / toluene; tetrahydrofuran / 1 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / 16 h 2.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 0 °C 2.2: 18 h / 10 - 20 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / -30 - -10 °C / Inert atmosphere; Cooling with acetone-dry ice |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 40 percent / NaH / dimethylsulfoxide / 24 h / Ambient temperature 2: 100 percent / ammonium formate / Pd/C / ethyl acetate / 1.5 h / 70 °C | ||
Multi-step reaction with 3 steps 1: 75 percent / aq. perchloric acid / 0.5 h / Ambient temperature 2: 55 percent / H2, triethylamine / Pd/C / ethyl acetate / 48 h / 76000 Torr / Ambient temperature 3: 97 percent / aq. potassium hydroxide / ethanol | ||
Multi-step reaction with 4 steps 1: pyridine / 0.5 h / Ambient temperature 2: mesyl chloride / pyridine / 3 h / Ambient temperature 3: 94.9 percent / H2 / 5percent Pd/C / ethyl acetate / 760 Torr / Ambient temperature 4: 97.6 percent / aq. NaOH / methanol / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 62 percent / 12 N HCl / 4 h / Ambient temperature 2: 85 percent / pyridine / 2.5 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: 99 percent / con. H2SO4, 4A molec. sieves / 1.5 h / Heating 2: 91 percent / pyridine / 1 h / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1: 85 percent / Nafion NR 50 / 20 h / Heating 2: 86 percent / Et3N / CH2Cl2 / 1) - 30 deg C, 5 min, 2) r.t., 2h |
Multi-step reaction with 2 steps 1.1: 1 h / 20 °C / Large scale 1.2: 10 °C / Large scale 2.1: pyridine / 4 h / -15 - 20 °C / Inert atmosphere; Large scale | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 10 °C / Large scale 2: pyridine / 4 h / -15 - 5 °C / Inert atmosphere; Large scale | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 72 h / 20 °C 2: triethylamine / dichloromethane / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 30 h / 20 °C 2: pyridine / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1.1: sulfuric acid / 12 h / 20 - 30 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / Inert atmosphere 2.2: 9 h / -20 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 84 percent / DMAP / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 30 min 7: 89 percent / 85percent m-chloroperoxybenzoic acid / CHCl3 / 96 h / Ambient temperature 8: 100 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / Ambient temperature | ||
Multi-step reaction with 8 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 84 percent / 4-dimethylaminopyridine / CH2Cl2 / 5 deg C, 1 h; 24 deg C, 30 min 7: 89 percent / m-chloroperoxybenzoic acid / CHCl3 / 96 h / 24 °C 8: 100 percent / H2 / 10 percent Pd/C / ethyl acetate / 0.5 h / 24 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature | ||
Multi-step reaction with 5 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 69 percent / NaH / dimethylformamide; paraffin / 3 h / Ambient temperature 7: 93 percent / n-Bu4NF / tetrahydrofuran / 3 h / Ambient temperature 8: 100 percent / NaH / dimethylformamide; paraffin / 2 h / Ambient temperature 9: 55 percent / 85percent MCPBA / CHCl3 / 24 h / Ambient temperature 10: 99 percent / DDQ, H2O / CH2Cl2 / 3 h / 24 °C | ||
Multi-step reaction with 10 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 69 percent / NaH / dimethylformamide / 3 h / 24 °C 7: 93 percent / Bu4NF / tetrahydrofuran / 3 h / 24 °C 8: 100 percent / NaH / dimethylformamide / 2 h / 24 °C 9: 55 percent / m-chloroperoxybenzoic acid / CHCl3 / 24 h / 24 °C 10: 99 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2; H2O |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h | ||
Multi-step reaction with 4 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h | ||
Multi-step reaction with 3 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 69 percent / NaH / dimethylformamide; paraffin / 3 h / Ambient temperature 7: 93 percent / n-Bu4NF / tetrahydrofuran / 3 h / Ambient temperature 8: 100 percent / NaH / dimethylformamide; paraffin / 2 h / Ambient temperature 9: 55 percent / 85percent MCPBA / CHCl3 / 24 h / Ambient temperature 10: 99 percent / DDQ, H2O / CH2Cl2 / 3 h / 24 °C 11: 99 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 12: 1.) Ph3P, 2.) H2O / 1.) THF, r.t., 9 d, 2.) 16 h | ||
Multi-step reaction with 12 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 69 percent / NaH / dimethylformamide / 3 h / 24 °C 7: 93 percent / Bu4NF / tetrahydrofuran / 3 h / 24 °C 8: 100 percent / NaH / dimethylformamide / 2 h / 24 °C 9: 55 percent / m-chloroperoxybenzoic acid / CHCl3 / 24 h / 24 °C 10: 99 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2; H2O 11: 99 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 12: 1.) PPh3; 2.) H2O / 1.) THF, 20-25 deg C, 7 d; 2.) THF, 24 deg C, 16 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 69 percent / NaH / dimethylformamide; paraffin / 3 h / Ambient temperature 7: 93 percent / n-Bu4NF / tetrahydrofuran / 3 h / Ambient temperature | ||
Multi-step reaction with 7 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 69 percent / NaH / dimethylformamide / 3 h / 24 °C 7: 93 percent / Bu4NF / tetrahydrofuran / 3 h / 24 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 84 percent / DMAP / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 30 min 7: 89 percent / 85percent m-chloroperoxybenzoic acid / CHCl3 / 96 h / Ambient temperature 8: 100 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / Ambient temperature 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C | ||
Multi-step reaction with 9 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 84 percent / 4-dimethylaminopyridine / CH2Cl2 / 5 deg C, 1 h; 24 deg C, 30 min 7: 89 percent / m-chloroperoxybenzoic acid / CHCl3 / 96 h / 24 °C 8: 100 percent / H2 / 10 percent Pd/C / ethyl acetate / 0.5 h / 24 °C 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 16 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 84 percent / DMAP / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 30 min 7: 89 percent / 85percent m-chloroperoxybenzoic acid / CHCl3 / 96 h / Ambient temperature 8: 100 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / Ambient temperature 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 10: 82 percent / p-TsOH*H2O / dimethylformamide / 16 h / Ambient temperature 11: 100 percent / NaH / dimethylformamide; paraffin / 1 h / Ambient temperature 12: 1.) PPh3, 2.) H2O / 1.) THF, 7 d, 2.) r.t. 13: 2percent HCl / methanol / 4 h / 50 °C 14: Et3N / tetrahydrofuran; H2O / 2 h / Ambient temperature 15: 1.) 2-chloro-3-ethylbenzoxazolium tetrafluoroborate, 2.) Et3N / 1.) MeCN, 0 deg C, 1 h, 2.) 0 deg C, 15 min 16: 43 percent / H2 / Pearlman's catalyst / methanol / 0.5 h / 60 °C / 760 Torr | ||
Multi-step reaction with 16 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 84 percent / DMAP / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 30 min 7: 89 percent / 85percent m-chloroperoxybenzoic acid / CHCl3 / 96 h / Ambient temperature 8: 100 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / Ambient temperature 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 10: 82 percent / p-TsOH*H2O / dimethylformamide / 16 h / Ambient temperature 11: 90 percent / NaH / dimethylformamide; tetrahydrofuran; paraffin / 16 h / Ambient temperature 12: 64 percent / 85percent aq. AcOH / 24 h / 40 - 45 °C 13: 89 percent / NaH / dimethylformamide; paraffin / 16 h / 10 °C 15: 1.) 2-chloro-3-ethylbenzoxazolium tetrafluoroborate, 2.) Et3N / 1.) MeCN, 0 deg C, 1 h, 2.) 0 deg C, 15 min; r.t., 30 min 16: 42 percent / H2 / Pearlman's catalyst / methanol / 0.5 h / 60 °C / 760 Torr | ||
Multi-step reaction with 15 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 84 percent / DMAP / CH2Cl2 / 1.) 0 deg C, 1 h, 2.) r.t., 30 min 7: 89 percent / 85percent m-chloroperoxybenzoic acid / CHCl3 / 96 h / Ambient temperature 8: 100 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / Ambient temperature 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 10: 82 percent / p-TsOH*H2O / dimethylformamide / 16 h / Ambient temperature 11: 1.) PPh3, 2.) H2O / 1.) THF, 5 d, 2.) r.t., 5 h 12: 2percent HCl / methanol / 2 h / 50 °C 13: Et3N / tetrahydrofuran; H2O / 2 h / Ambient temperature 14: 1.) 2-chloro-3-ethylbenzoxazolium tetrafluoroborate, 2.) Et3N / 1.) MeCN, 0 deg C, 1 h, 2.) 0 deg C, 5 min 15: 46 percent / H2 / Pearlman's catalyst / methanol / 0.5 h / 60 °C / 760 Torr |
Multi-step reaction with 16 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature 3: 43 percent / DABCO / dimethylformamide / 1 h 5: 99 percent / CeCl3*7H2O, NaBH4 / ethanol / 0.5 h / Ambient temperature 6: 69 percent / NaH / dimethylformamide; paraffin / 3 h / Ambient temperature 7: 93 percent / n-Bu4NF / tetrahydrofuran / 3 h / Ambient temperature 8: 100 percent / NaH / dimethylformamide; paraffin / 2 h / Ambient temperature 9: 55 percent / 85percent MCPBA / CHCl3 / 24 h / Ambient temperature 10: 99 percent / DDQ, H2O / CH2Cl2 / 3 h / 24 °C 11: 99 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 12: 1.) Ph3P, 2.) H2O / 1.) THF, r.t., 9 d, 2.) 16 h 13: 2percent HCl / methanol / 3 h / 50 °C 14: Et3N / tetrahydrofuran; H2O / 2 h / Ambient temperature 15: 1.) 2-chloro-3-ethylbenzoxazolium tetrafluoroborate, 2.) Et3N / 1.) MeCN, 0 deg C, 2 h, 2.) 0 deg C, 30 min 16: 37 percent / H2 / Pearlman's catalyst / methanol / 0.5 h / 60 °C / 760 Torr | ||
Multi-step reaction with 16 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 84 percent / 4-dimethylaminopyridine / CH2Cl2 / 5 deg C, 1 h; 24 deg C, 30 min 7: 89 percent / m-chloroperoxybenzoic acid / CHCl3 / 96 h / 24 °C 8: 100 percent / H2 / 10 percent Pd/C / ethyl acetate / 0.5 h / 24 °C 9: 92 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 10: 80 percent / TsOH / dimethylformamide / 16 h / 24 °C 11: 100 percent / NaH / dimethylformamide / 1 h / 24 °C 12: 1.) PPh3; 2.) H2O / 1.) THF, 24 deg C, 7 d; 2.) THF, 24 deg C, 10 h 13: 2 percent HCl / methanol / 4 h / 50 °C 14: Et3N / tetrahydrofuran; H2O / 2 h / 24 °C 15: 71 percent / 2-chloro-3-ethylbenzoxazolium tetrafluoroborate / acetonitrile / 0 - 5 °C 16: 42 percent / H2 / Pd(OH)2/C / methanol / 1 h / 60 °C | ||
Multi-step reaction with 16 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide 3: 43 percent / DABCO / dimethylformamide / 1 h / 0 - 5 °C 4: 46 percent / tetrahydrofuran / -78 deg C, 15 min; 24 deg C, 17 h 5: 89 percent / NaBH4, CeCl3*7H2O / ethanol / 0.5 h / 24 °C 6: 69 percent / NaH / dimethylformamide / 3 h / 24 °C 7: 93 percent / Bu4NF / tetrahydrofuran / 3 h / 24 °C 8: 100 percent / NaH / dimethylformamide / 2 h / 24 °C 9: 55 percent / m-chloroperoxybenzoic acid / CHCl3 / 24 h / 24 °C 10: 99 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2; H2O 11: 99 percent / NaN3, NH4Cl / dimethylformamide / 16 h / 100 °C 12: 1.) PPh3; 2.) H2O / 1.) THF, 20-25 deg C, 7 d; 2.) THF, 24 deg C, 16 h 13: 2 percent HCl / methanol / 3 h / 50 °C 14: Et3N / tetrahydrofuran; H2O / 2 h / 24 °C 15: 1.) 2-chloro-3-ethylbenzoxazolium tetrafluoroborate; 2.) Et3N / 1.) MeCN, 0-5 deg C, 2 h; 2.) MeCN, 0 deg C, 30 min; 24 deg C, 30 min 16: 37 percent / H2 / Pd(OH)2/C / methanol / 0.5 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 2.) 1 M aq. HCl / 1.) pyridinium p-toluenesulfonate / 1.) 50 deg C, 1 h, 2.) THF, 24 - 25 deg C, 1 h 2: 95 percent / Dess-Martin reagent / CH2Cl2 / 0.5 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: 1.) pyridinium p-toluenesulfonate, 2.) 1 M HCl / 1.) DMF, 50 deg C, 1 h; 2.) THF, 1 h 2: 80 percent / DCC, H3PO4 / dimethylsulfoxide | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 20 °C 2: Dess-Martin periodane / dichloromethane / 0.5 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 92 percent / I2 / 12 h / Ambient temperature 2: 82 percent / imidazole / dimethylformamide / 2.5 h / 60 °C 3: 72 percent / 80percent aq. AcOH / 1.5 h / Heating 4: 96 percent / acetone / 2.5 h / Heating 5: 96 percent / Raney Ni / tetrahydrofuran / 2.5 h / Heating | ||
Multi-step reaction with 3 steps 1: 5 percent / imidazole / dimethylformamide / 0.5 h / Ambient temperature 2: 96 percent / acetone / 2.5 h / Heating 3: 96 percent / Raney Ni / tetrahydrofuran / 2.5 h / Heating | ||
Multi-step reaction with 3 steps 3: Raney nickel / tetrahydrofuran / Heating |
Multi-step reaction with 3 steps 1: 84 percent / imidazole / dimethylformamide / Ambient temperature 2: 85 percent / acetone / 1 h / Heating 3: 82 percent / Raney nickel / acetone / 1.5 h / Heating | ||
Multi-step reaction with 6 steps 1: imidazole / dimethylformamide / 1 h / -20 - -15 °C 2: tetrahydrofuran / 0.25 h / Ambient temperature 3: Raney nickel / tetrahydrofuran / 4 h / Heating 4: 71.5 percent / triethylamine, 4,4-dimethylaminopyridine / CH2Cl2 / 3.5 h / Ambient temperature 5: 1.) lithium hexamethyldisilazide / 1.) THF, hexane, -78 deg C, 25 min; 2.) THF, hexane 6: 30percent H2O2 / 0 °C | ||
Multi-step reaction with 3 steps 1: imidazole / dimethylformamide / 1 h / -20 - -15 °C 2: tetrahydrofuran / 0.25 h / Ambient temperature 3: Raney nickel / tetrahydrofuran / 4 h / Heating | ||
Multi-step reaction with 2 steps 1: methyltrioxorhenium(VII) / 15 h / 170 - 180 °C / Sealed tube; Inert atmosphere 2: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 92 percent / I2 / 12 h / Ambient temperature 2: 82 percent / imidazole / dimethylformamide / 2.5 h / 60 °C 3: 72 percent / 80percent aq. AcOH / 1.5 h / Heating 4: 96 percent / acetone / 2.5 h / Heating 5: 96 percent / Raney Ni / tetrahydrofuran / 2.5 h / Heating 6: 1.) CuBr, Me2S / 1.) Et2O, -78 deg C, 10 min, 2.) Et2O, a) -78 deg C, 30 min, b) RT, 5 min | ||
Multi-step reaction with 4 steps 1: 5 percent / imidazole / dimethylformamide / 0.5 h / Ambient temperature 2: 96 percent / acetone / 2.5 h / Heating 3: 96 percent / Raney Ni / tetrahydrofuran / 2.5 h / Heating 4: 1.) CuBr, Me2S / 1.) Et2O, -78 deg C, 10 min, 2.) Et2O, a) -78 deg C, 30 min, b) RT, 5 min | ||
Multi-step reaction with 7 steps 1: imidazole / dimethylformamide / 1 h / -20 - -15 °C 2: tetrahydrofuran / 0.25 h / Ambient temperature 3: Raney nickel / tetrahydrofuran / 4 h / Heating 4: 71.5 percent / triethylamine, 4,4-dimethylaminopyridine / CH2Cl2 / 3.5 h / Ambient temperature 5: 1.) lithium hexamethyldisilazide / 1.) THF, hexane, -78 deg C, 25 min; 2.) THF, hexane 6: 30percent H2O2 / 0 °C 7: 1.) CuBr*Me2S / 1.) ether, hexane, 0 deg C, 6 min; 2.) -23 deg C, 20 min. |
Multi-step reaction with 4 steps 1: imidazole / dimethylformamide / 1 h / -20 - -15 °C 2: tetrahydrofuran / 0.25 h / Ambient temperature 3: Raney nickel / tetrahydrofuran / 4 h / Heating 4: 1.) CuBr*Me2S / 1.) ether, hexane, 0 deg C, 6 min; 2.) -23 deg C, 20 min. | ||
Multi-step reaction with 3 steps 1.1: methyltrioxorhenium(VII) / 15 h / 170 - 180 °C / Sealed tube; Inert atmosphere 2.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 0 - 20 °C / Inert atmosphere 3.1: copper(l) iodide / diethyl ether / 0 °C / Inert atmosphere 3.2: 1 h / Inert atmosphere; Cooling |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: conc. HCl 2: NaH / dimethylformamide 3: n-Bu3SnH, AIBN / toluene / Heating 4: aq. CF3CO2H / CHCl3 / Heating 5: CBr4, PPh3 / acetonitrile | ||
Multi-step reaction with 2 steps 1: 36 percent / HBA / 60 h 2: H2, triethylamine / palladium-on-carbon / ethyl acetate | ||
Multi-step reaction with 4 steps 1: conc. HCl / 7 h / Ambient temperature 2: 1. sodium hydride / 1. dimethylformamide, room temperature, 30 min 2. 30 min, room temperature 3: 92.5 percent / tri-n-butyltin hydride, AIBN / toluene / 2 h / Heating 4: 1. CF3COOH 2. CBr4, PPh3 / 1. CHCl3, H2O, 10 h, reflux |
Multi-step reaction with 3 steps 1: 52 percent / pyridine / 6 h / -20 - -10 °C 2: LiBr / acetone 3: 53 percent / NaI, TFA / acetone | ||
Multi-step reaction with 3 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: hydrogen, triethyl amine / Pd/C / ethyl acetate 3: carbon tetrabromide, triphenyl phosphine / acetonitrile | ||
Multi-step reaction with 5 steps 1: 92.7 percent / hydrochloric acid / 7 h 2: 1.) sodium hydride / 1.) DMF, sodium hydride 3: 92.5 percent / tri-n-butyltin hydride / toluene / Heating 4: CHCl3; trifluoroacetic acid; H2O / 10 h / 70 °C 5: carbon tetrabromide, triphenyl phosphine / acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 84 percent / pyridine / 16 h / 70 °C 2: 79 percent / acetone / 3.5 h / Heating 3: 1.) Ni(Ra), acetone / 1.) reflux, overnight, 2.) THF, reflux, 24 h 4: 1.) cuprous bromide, dimethyl sulfide / 1.) ether, 0 deg C, 15 min, 2.) benzene, 1 h 5: 76 percent / H2SO4, H2 / Pd/C / ethanol / 24 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 84 percent / pyridine / 16 h / 70 °C 2: 79 percent / acetone / 3.5 h / Heating 3: 1.) Ni(Ra), acetone / 1.) reflux, overnight, 2.) THF, reflux, 24 h 4: 1.) cuprous bromide, dimethyl sulfide / 1.) ether, 0 deg C, 15 min, 2.) benzene, 1 h 5: 76 percent / H2SO4, H2 / Pd/C / ethanol / 24 h / Ambient temperature 6: Et3N / CH2Cl2 / 0.25 h / 0 °C 7: LiBr / tetrahydrofuran / 4 h / Heating 8: 86 percent / Li, NH3 / tetrahydrofuran / 2 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 84 percent / pyridine / 16 h / 70 °C 2: 79 percent / acetone / 3.5 h / Heating 3: 1.) Ni(Ra), acetone / 1.) reflux, overnight, 2.) THF, reflux, 24 h | ||
Multi-step reaction with 2 steps 2: 50 percent / pyridine / CH2Cl2 / 4 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: pyridine, Me2NPy / 4 h / Ambient temperature 2: pyridine, Me2NPy / 2 h / Ambient temperature 3: Et3N / benzene / 2 h / Heating | ||
Multi-step reaction with 2 steps 1: 96 percent / imidazole / dimethylformamide / 1.) 65-70 deg C, 5 h, 2.) room temperature, overnight 2: DBU / benzene / 0.5 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 84 percent / pyridine / 16 h / 70 °C 2: 79 percent / acetone / 3.5 h / Heating 3: 1.) Ni(Ra), acetone / 1.) reflux, overnight, 2.) THF, reflux, 24 h 4: 1.) cuprous bromide, dimethyl sulfide / 1.) ether, 0 deg C, 15 min, 2.) benzene, 1 h 5: 76 percent / H2SO4, H2 / Pd/C / ethanol / 24 h / Ambient temperature 6: Et3N / CH2Cl2 / 0.25 h / 0 °C 7: LiBr / tetrahydrofuran / 4 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 84 percent / pyridine / 16 h / 70 °C 2: 79 percent / acetone / 3.5 h / Heating 3: 1.) Ni(Ra), acetone / 1.) reflux, overnight, 2.) THF, reflux, 24 h 4: 1.) cuprous bromide, dimethyl sulfide / 1.) ether, 0 deg C, 15 min, 2.) benzene, 1 h 5: 76 percent / H2SO4, H2 / Pd/C / ethanol / 24 h / Ambient temperature 6: Et3N / CH2Cl2 / 0.25 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With methyltrioxorhenium(VII) at 170 - 180℃; for 15h; Sealed tube; Inert atmosphere; | |
Multi-step reaction with 2 steps 1: 1.) THF, 12 h, reflux, 2.) 7 d 2: 68 percent / 220 °C / 40 Torr | ||
Multi-step reaction with 2 steps 1: tetrahydrofuran / 12 h / Heating 2: 68 percent / 220 °C / 40 Torr |
23.5 mg | With methyltrioxorhenium(VII) at 155℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 1.) THF, 12 h, reflux, 2.) 7 d 2: 68 percent / 220 °C / 40 Torr 3: 71 percent / pyridine / CH2Cl2 / 14 h / Ambient temperature 4: 63 percent / NaI / acetone / 8 h / Heating 5: 63 percent / CaCO3 / Ni-Ra W-4 / ethanol / 2 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: conc. HCl / 7 h / Ambient temperature 2: 1. sodium hydride / 1. dimethylformamide, room temperature, 30 min 2. 30 min, room temperature 3: 92.5 percent / tri-n-butyltin hydride, AIBN / toluene / 2 h / Heating 4: 1. CF3COOH 2. CBr4, PPh3 / 1. CHCl3, H2O, 10 h, reflux 5: 91.7 percent / tri-n-butyltin hydride, AIBN / toluene / 18 h / 90 °C | ||
Multi-step reaction with 4 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: hydrogen, triethyl amine / Pd/C / ethyl acetate 3: carbon tetrabromide, triphenyl phosphine / acetonitrile 4: 91.7 percent / tri-n-butyltin hydride / toluene / Heating | ||
Multi-step reaction with 4 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: hydrogen, triethyl amine / Pd/C / ethyl acetate 3: carbon tetrabromide, triphenyl phosphine / acetonitrile 4: hydrogen, triethyl amine / Pd/C / ethyl acetate |
Multi-step reaction with 3 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: carbon tetrabromide, triphenyl phosphine / acetonitrile 3: tri-n-butyltin hydride / toluene / Heating | ||
Multi-step reaction with 2 steps 1: 1.) hydrogen bromide, 2.) methanol / 1.) acetic acid, 4 h, rt 2: tri-n-butyltin hydride / toluene / Heating | ||
Multi-step reaction with 6 steps 1: 92.7 percent / hydrochloric acid / 7 h 2: 1.) sodium hydride / 1.) DMF, sodium hydride 3: 92.5 percent / tri-n-butyltin hydride / toluene / Heating 4: CHCl3; trifluoroacetic acid; H2O / 10 h / 70 °C 5: carbon tetrabromide, triphenyl phosphine / acetonitrile 6: 91.7 percent / tri-n-butyltin hydride / toluene / Heating | ||
Multi-step reaction with 6 steps 1: 92.7 percent / hydrochloric acid / 7 h 2: 1.) sodium hydride / 1.) DMF, sodium hydride 3: 92.5 percent / tri-n-butyltin hydride / toluene / Heating 4: CHCl3; trifluoroacetic acid; H2O / 10 h / 70 °C 5: carbon tetrabromide, triphenyl phosphine / acetonitrile 6: hydrogen, triethyl amine / Pd/C / ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.6 g (43%) | With sulfuric acid; ammonia In chloroform; acetone; Petroleum ether | 2.A A. A. Preparation of Ribonic acid-gamma-lactone dimethyl ketal A solution of 215.0 g (0.17 mol) of ribonic acid-gamma-lactone in 500 ml. of acetone was stirred in an ice bath, while 10 mL of concentrated sulfuric acid was added. The reaction was stirred at ambient temperature for 5 hours. Ammonia (gas) was bubbled through the cooled solution causing a precipitate to form. The mixture was filtered and excess acetone was removed in vacuo. The material was crystallized using chloroform/petroleum ether to give 11.6 g (43%) of product: m.p. 135-137; NMR: (CDCl3) δ 4.7 (s, 2H), 4.5 (t, 1H), 3.8 (m, 2H), 2.8 (s, 1H), 1.5 (s, 3H), 1.4 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In N,N-dimethyl-formamide at 20℃; for 1h; | |
In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In N,N-dimethyl-formamide at 20℃; for 1h; | |
In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.9% | With sodium iodide In methanol; acetone at 20℃; | 3.2.4. d-Ribono-1,4-lactone·NaI (2c) To a solution of d-ribono-1,4-lactone (0.44 g, 3 mmol) in a mixture of acetone (5 mL) and MeOH (1 mL) sodium iodide (0.45 g, 3 mmol) was added under stirring at room temperature. Under continuous stirring solids dissolved within some minutes. Solvents were removed by distillation under reduced pressure and the crystalline residue was re-dissolved in acetone (5 mL). Dilution with ethyl acetate (15 mL) resulted in slow separation of pure 1c in white crystals (0.64 g, 71.9%), mp 71-72 °C; [α]D +12.3 (H2O, c 4). Calcd for 2C5H8O5·NaI·H2O [α]D +11.7. Anal. Calcd for C10H18INaO11 (464.14): I, 27.34. Found: I, 27.13. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With Candida antarctica lipase B In acetonitrile at 35℃; for 24h; Enzymatic reaction; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With Candida antarctica lipase B In acetonitrile at 35℃; for 24h; Enzymatic reaction; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With dmap; triethylamine In dichloromethane at 0℃; Inert atmosphere; | 1.S2; 2.S2; 3.S2 S2, the preparation of compound RD-2 Weigh 70g, 0.5mol of compound RD-1, 350g of dichloromethane, 0.6g, 0.005mol, 0.01eq of 4-dimethylaminopyridine,48.5g, 0.475mol, 0.95eq of acetic anhydride;First, compound RD-1, dichloromethane and 4-dimethylaminopyridine were fully stirred and dissolved according to the above-mentioned weighing amount,Then add 2 mL of triethylamine,Cool down to 0°C, under nitrogen protection,Add acetic anhydride dropwise, stir for 1-2 hours,Under the monitoring of TLC, the incubation reaction was carried out for 4 to 6 hours (as shown in Figure 2),Then add 2M hydrochloric acid for 1 hour quenching at -55,washed with saturated aqueous sodium bicarbonate solution,washed,Concentration gave 77 g of compound RD-2 as an oily substance, and the yield was 80%. |
With Candida antarctica lipase B In acetonitrile at 35℃; for 6h; Enzymatic reaction; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Candida antarctica lipase B In ethanol at 35℃; for 6h; Enzymatic reaction; regioselective reaction; | Determination of the catalyst amount for the alcoholysis of 3 The optimal amount of CAL-B was determined by reacting 2,3,5-tri-O-acetyl-D-ribonolactone (3, 0.5 mmol) in EtOH (5.0 mL) using 18, 35, 70, 140, and 280 mg of the biocatalyst in a temperature-controlled incubator shaker (150 rpm, 35 °C). After 6 h, each supernatant solution was decanted, the enzyme was washed with 3 mL of MeOH followed by 3 mL of ACN and the solvent removed under reduced pressure. The light yellow oil obtained was then analyzed by 1H NMR to determine the amount of 2,3-di-O-acetyl-D-ribonolactone (4) produced in each case (Table 5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With hydrogen; per-rhenic acid In 1,4-dioxane at 150℃; | Development of an effective DODH strategy to produce a DODH adduct lactone product from oxidized derivatives of glucose using I2 as a reducing agent. It was found that the unsaturated analog of levulinic acid could be isolated in moderate to good yield by performing a reaction with ribonolactone, a catalytic amount of HReO4 in dioxanes at 150°C and under 150 psi of H2 gas (see FIG. 4). It is theorized, but not relied upon, that this reaction occurs through a DODH reaction followed by an elimination reaction to generate protoanemonin. Under the reactions conditions, protoanemonin undergoes ring opening with residual water and subsequent olefin isomerization leads to the observed product. No reaction was observed when xylonolactone was exposed to the same reaction conditions. This was not surprising considering previous literature has shown that DODH reactions with cyclic diols require the syn stereochemistry found within ribonolactone, which is not present in xylonolactone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With palladium on activated charcoal; hydrogen; methyltrioxorhenium(VII) at 150℃; | General procedure: The above further illustrates the substrate selectivity of the disclosed DODH method.Tn another experiment, a transformation to adipic acid in one pot was acheived, without adding additional catalyst, by regenerating the catalyst in situ by reoxidation with oxygen. As shown in the following reaction scheme, iteratively repeating the atmosphere exchange cycles, the yield of adipic acid was improved. The hydrogenation step is conducted at elevated H2 pressure; whereas the DODH chemistry is conducted at low H2 pressure |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 75% 2: 22% | With potassium perrhenate; phosphoric acid; palladium on activated charcoal; hydrogen; pyrographite at 150℃; | The table above demonstrates the significant yield improvements achieved by the addition of charcoal. The yield of adipate was improved to 91% from 70% by addition of activated charcoal, while the same ease of use (no atmosphere exchange, all reactions to the adipate carried out under the same set of conditions) was maintained. The catalyst system is also competent in the transformation of other diols in ctj3-position to carboxylate moieties as demonstrated in the table above. The final example in the table, i.e., 1,5-gluconolactone, demonstrates this selectivity within a single molecule: only the ctj3-diol group is transformed. The other hydroxy functionalities are not affected.[0136] A Parr reactor charged with polyol (7.5 mmol), KReO4 (22 mg), 10% Pd/C (60 mg), 85% H3P04 (26 mg), granular activated carbon (450 mg, C270C, purchased from Fisher), and MeOH (7.5 mL) was pressurized to 75 psi with H2. The reaction was placed in a preheated oil bath set to 150°C for a given amount of time until the reaction was complete (typically from a few hours up to three days). The reaction mixture was cooled to room temperature, filtered, rinsed with MeOH, and concentrated |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With water In methanol at 50℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With trifluorormethanesulfonic acid; silica gel In acetonitrile at 50℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: D-Ribono-1,4-lactone With sodium hydride In N,N-dimethyl-formamide at -10℃; for 1h; Inert atmosphere; Stage #2: 2-bromomethylnaphthyl bromide In N,N-dimethyl-formamide at -10℃; for 48.5h; | 4 Preparation of compound 3-1b: Starting material 3 (5.0 g, 33.76 mmol) [prepared according to the method of Org. Synth. 2005, 82, 75-79] was dissolved in anhydrous DMF (200 mL).Protected with nitrogen and cooled to -10 ° C,Slowly add 60% NaH (1.8 g, 43.89 mmol),After stirring at -10 ° C for 1 hour,2-Bromomethylnaphthalene (11.2 g, 50.64 mmol) was slowly added.After stirring for another 30 minutes,Add 60% NaH (1.8g, 43.89mmol) as above.And 2-bromomethylnaphthalene (11.2 g, 50.64 mmol),Repeat twice, keep the temperature at -10 ° C and stir the reaction for 48 hours.The reaction solution was poured into 500 mL of ice water to quench the reaction and extracted with ethyl acetate (100 mL×4).The organic layer was combined and washed with brine (2 mL)Concentrated, silica gel column separation (10:1, V/V, petroleum ether: EtOAc)The white oily product 3-1b (13.8 g, 24.31 mmol),Yield: 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: D-Ribono-1,4-lactone With sodium hydride In N,N-dimethyl-formamide at -10℃; for 1h; Inert atmosphere; Stage #2: 2-bromomethylnaphthyl bromide In N,N-dimethyl-formamide at -10℃; for 48.5h; Inert atmosphere; | 12 Preparation of compound 2-1d: Starting material 6-1d (5.0 g, 33.76 mmol) was dissolved in anhydrous DMF (200 mL). Protected with nitrogen and cooled to -10 ° C, Slowly add 60% NaH (1.8 g, 43.89 mmol), After stirring at -10 ° C for 1 hour, 2-Bromomethylnaphthalene (11.2 g, 50.64 mmol) was slowly added. After stirring for another 30 minutes, Further, 60% NaH (1.8 g, 43.89 mmol) and 2-bromomethylnaphthalene (11.2 g, 50.64 mmol) were added as above. Repeat twice, keep the temperature at -10 ° C and stir the reaction for 48 hours. The reaction solution was poured into 500 mL of ice water to quench the reaction. Extracted with ethyl acetate (100 mL x 4), Combine the organic phase, The organic layer was washed with 200 mL of saturated brine. Dry over anhydrous sodium sulfate, concentrate, Separation on silica gel column (10:1, V/V, petroleum ether: EtOAc) The product 2-1d (13.8 g, 24.31 mmol) was obtained as white oil. Yield: 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With iodine In dichloromethane at 15 - 30℃; for 4h; | 5; 6; 15 Example 15 Weigh 10g of D-(+)-ribonate-1,4-lactone shown in formula 5 into a 500mL three-necked flask, add 0.05g iodine, 80mL dichloromethane, stir and cool to 15-20, add dropwise 19.5g of bis(trimethylsilyl)amine (HMDS) trimethylsilyl, the control temperature is less than 22°C.After dropping, the temperature was raised to 30°C and reacted for 4h. After the reaction, the temperature was lowered to 10°C, and 2 g of activated carbon with a particle size of 50 µm was added for 5 hours to decolorize, and filtered. The filtrate was light yellow with a purity of 96.5%.Concentrate the organic phase to obtain an oil, and then distill the oil in a high vacuum to obtain the product represented by formula 6. The purity is 97%, and the yield is 77%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 12% 2: 55% | With zinc(II) chloride In 1,2-dimethoxyethane at 20℃; for 5h; Inert atmosphere; | 3.5. 2,3-O-(R)-Benzylidene-D-Ribono-1,4-Lactone (11R) and2,3-O-(S)-Benzylidene-D-Ribono-1,4-Lactone (11S) Method A: D-(+)-ribono-1,4-lactone 2 (1.00 g, 6.75 mmol) was suspended with vigorousstirring in dry 1,2-dimethoxyethane (3 mL)-containing benzaldehyde (5 mL, 49.23 mmol),then ZnCl2 (0.90 g, 6.60 mmol) was added, and the mixture was stirred at room temperatureunder an argon atmosphere. After 5 h, water (5 mL) was added and the mixture wasextracted with AcOEt (3 5 mL), the organic layer was washed with water and aqueousNaHCO3, dried over anhydrous Na2SO4 and evaporated in vacuum. The residue waspurified by flash chromatography on silica gel (hexane/AcOEt 6:4 v:v) to afford the compounds11R (877 mg, 55% yield) and 11S (191 mg, 12% yield) as white solids. Compound 11R showed: TLC (hexane/AcOEt 7:3 v:v) Rf 0.13; mp 164-165 C, [lit. [30] 156-158 C, [34]163-164 C]; []22D 78.0 (c 0.5, CHC13) [lit. [30] 79.1 (c 0.56, CHC13) 70 (DMF)].Compound 11S showed: TLC (hexane/AcOEt 7:3 v:v) Rf 0.21; mp 86-87 C [lit. [31]83-84 C, [34] 87-88 C]; []22D 38 (c 1.0, CHC13) [lit. [31] 39.3 (c 1.16, CHC13), [34]40 (CHC13)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; pyridinium chlorochromate In tetrahydrofuran at 0 - 5℃; Inert atmosphere; | 1.S1; 2.S1; 3.S1 S1. Preparation of compound RD-1 Weigh 100g, 0.67mol of D-ribose,25.5g, 0.165mol, 0.25eq of diazabicyclo, 500ml of tetrahydrofuran, 158g, 0.73mol, 1.1eq of pyridinium chlorochromate;First, the D-ribose, diazabicyclo and tetrahydrofuran are fully stirred and dissolved according to the above-mentioned weighing amount,Under the protection of nitrogen,Cool down to 05,Then slowly add pyridinium chlorochromate in batches,The reaction was carried out for 2-3 hours under TLC monitoring (as shown in Figure 1),After the reaction is over,Add 6.5g, 62.5mmol of sodium hydrogen sulfite to quench under the condition of 05 , after stirring for 30 minutes,Concentrate under vacuum at 45 to 50 °C to form a reaction solution, and then use anhydrous ethanol for hot filtration.Concentrated to obtain 85g of white solid compound RD-1,The yield was 86%. |
Tags: 5336-08-3 synthesis path| 5336-08-3 SDS| 5336-08-3 COA| 5336-08-3 purity| 5336-08-3 application| 5336-08-3 NMR| 5336-08-3 COA| 5336-08-3 structure
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P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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