Structure of 220798-39-0
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CAS No. : | 220798-39-0 |
Formula : | C8H10O3S |
M.W : | 186.23 |
SMILES Code : | CS(=O)(=O)C1=CC=CC(CO)=C1 |
MDL No. : | MFCD15527275 |
InChI Key : | XFMFNVYEANZUHC-UHFFFAOYSA-N |
Pubchem ID : | 23549738 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.75 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.32 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.51 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.96 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.9 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.05 |
Solubility | 16.6 mg/ml ; 0.0891 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.57 |
Solubility | 50.4 mg/ml ; 0.27 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.54 |
Solubility | 0.537 mg/ml ; 0.00288 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.64 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.78 |
* 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 |
---|---|---|
90% | With borane-THF; In tetrahydrofuran; at 20℃; for 12h; | A solution of 3- (methylsulfonyl) benzoic acid (1.0 g, 5.0 mmol) in anhydrous THF (25 mL) was treated with BH3. THF (1 M solution, 7.5 mL) at room temperature. The reaction was stirred for 12 hours before it was quenched by slow addition of MeOH. The solvent was removed and the residue was purified by flash column chromatography (0-5 % MeOH in CH2CI2) to give the product (0.84 g, 90% yield NMR (300 MHz, CDCI3) 5 : 3.06 (s, 3 H), 4.81 (d, J = 6.0 Hz, 2 H), 7.54-7. 59 (m, 1 H), 7. 65-7.68 (m, 1 H), 7.85-7. 88 (m, 1 H), 7.96 (s, 1 H). |
63% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 15℃; for 14h; | To a solution of 34 (2.00 g , 9.99 mmol) in THF (10 mL) was added UAIH4(758 mg, 20.0 mmol) at 0 C. The mixture was stirred at 15 C for 14 h. The mixture was cooled to 0 C and quenched by saturated solution of potassium sodium tartrate (2mL), the precipitate formed was collected, filtered to remove the precipitate. The organic phase was concentrated in vacuo to give 35 (1 .40 g, 63%).1H N R (400 MHz, CDCI3) 7.97 (s, 1 H), 7.87 (d, J - 7.5 Hz, 1 H), 7.67 (d, J - 7.9 Hz, 1 H), 7.63 - 7.53 (m, 1 H), 4.82 (d , J = 5.7 Hz, 2H), 3.07 (s, 3H). |
51% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; | (13A) [3-(Methylsulfonyl)phenyl]methanol 3-(Methylsulfonyl)benzoic acid (540 mg, 2.70 mmol) was dissolved in tetrahydrofuran (40 mL), and the resulting solution was cooled to 0 C. Then, lithium aluminum hydride (102 mg, 2.70 mmol) was added thereto, and the temperature of the resulting mixture was raised to room temperature, and the mixture was stirred for 3 hours. Water was added to the reaction solution, and the organic matter was extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution, then dried over anhydrous magnesium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 70:30 (v/v)), whereby the objective title compound was obtained as a colorless oily substance (257 mg, yield: 51%). 1H NMR (CDCl3, 400 MHz): delta1.26 (1H, brs), 3.06 (3H, s), 4.81 (2H, d, J=5.5 Hz), 7.57 (1H, t, J=7.8 Hz), 7.67 (1H, d, J=7.5 Hz), 7.86 (1H, d, J=7.5 Hz), 7.96 (1H, s) |
42% | With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; for 1h;Heating / reflux; | To an ice-cold solution of 3- (methylsulfonyl) benzoic acid (1.4 g, 7.1 mmol) in 2: 1 Et20/THF (60 mL) was added LIALH4 (8.5 mL of 1.0 M solution in THF, 8.5 mmol), and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled to 0 C, and the reaction was quenched with water (15 mL) and 15% NaOH in water (35 mL). The reaction mixture was filtered, concentrated under reduced pressure, and the residue was dissolved in EtOAc. The organic solution was washed with water and then brine, dried (MGS04), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 1: 2 to 3: 1 EtOAc/hexanes) provided (3- methanesulfonyl) phenyl methanol as a clear oil (0.56 g, 42%) :H NMR (300 MHz, CDC13) 5 7.93 (s, 1H), 7.83 (d, J = 7 Hz, 1H), 7.64 (d, J = 7 Hz, 1H), 7.53 (t, J = 7 Hz, 1H), 4. 78 (d, J = 6 Hz, 2H), 3.05 (s, 3H), 2.61 (br s, 1H). |
With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 0.166667h; | To an ice-cooled stirring solution of 1M BH3 in THF (25 ml_, 25 mmol) under inert atmosphere is added dropwise over a 10 minutes period a solution of 3- methanesulfonylbenzoic acid (2g, 10 mmol) in THF (20 mL). The reaction mixture is stirred at room temperature overnight then cooled down to 0C before adding water (2 mL). The solvent is removed under reduced pressure and the residue is partitioned between DCM and NaOH. The organic layer is isolated and dried over MgSO4 and filtered. The solvent is removed under reduced pressure to give (3-methanesulfonyl-phenyl)-methanol; [M-H]' 185. | |
With borane-THF; In tetrahydrofuran; at 0 - 20℃; | (3-Methanesulfonyl-phenyl)-methanol was prepared as follows: To 3- Methanesulfonyl-benzoic acid in THF at O0C was added dropwise a borane-THF complex and the reaction mixture stirred at room temperature overnight. Excess hydride was destroyed by slow addition of a water/THF mixture. The aqueous phase was saturated with potassium carbonate then extracted with ether. The organics were dried with MgSO4 and the solvent reduced in vacuo to yield (3-methanesulfonyl-phenyl)- methanol as a clear oil. | |
Borane solution (1M in THF) was added dropwise to a stirred mixture of 3-methylsulfonyl)benzoic acid (400 mg, 2.00 mmol) in anhydrous THF (2 ml) at 0 C. The resulting mixture was then allowed to warm to room temperature and stirred for 3 h. The reaction mixture quenched with water/1 M HCl (aq.), extracted with ethyl acetate (3 times), the combined organic extracts dried (sodium sulfate) and concentrated in vacuo to give crude (3-(methylsulphonyl)phenyl)methanol as an oil which was used in the next step without further purification. The alcohol was dissolved in dichloromethane (6 ml) and triethylamine (0.418 mL, 3.0 mmol). Methanesulfonylchloride (first batch (0.186 mL, 2.4 mmol) was then added, followed by a second batch (0.039 mL, 0.5 mmol) and the resulting mixture was stirred for 16 h. 1 N HCl solution (aq.) was then added and the reaction mixture was extracted with diethyl ether (3 times), the combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by column chromatography eluting using a gradient (petroleum ether 40/60/ethyl acetate 1:0 v/v 0:1) to afford 212 mg (52% over 2 steps) of the title compound as an oil. 1H NMR (CDCl3): 7.98 (1H, s), 7.91 (1H, d, J 7.8), 7.70 (1H, d, J 7.8), 7.59 (1H, t, J 7.8), 4.65 (2H, s), 3.08 (s, 3H). | ||
To a solution of Intermediate AX (l.Og, 4.99 mmol) in THF (20mL) at 0 C was added a solution of BH3DMS (0.94 mL, 9.98 mmol). After the addition was complete, the reaction mixture was stirred at 70 C for 1 hour. The reaction mixture was cooled, methanol (5.0 mL) was added, and the mixture was refluxed for 30 minutes. Solvent from the reaction mixture was removed via distillation, and the residue was diluted with ethyl acetate (30 mL), washed with water (2 x 15 mL) and brine (15 mL), dried over dried over anhydrous Na2S04, and the solvent was removed to afford the crude Intermediate AY (720mg, 77%) as an off white solid. This material was used in the next step without further purifications. NMR (CDC13): delta 7.95 (s, 1H), 7.85 (d, J = 7.88 Hz; 1H), 7.66 (d, J= 7.88 Hz, 1H), 7.56 (t, J= 7.65 Hz; 1H), 4.80 (s, 2H), 3.06 (s, 3H). Mass (M+H): 187.0. | ||
With borane-THF; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0 - 20℃; | To a solution of 3-(methylsulfonyl)benzoic acid (1.2 g, 6:0 mmol) in THF (30 ml.) at 0 0C, is added equimolar amounts of borane (6.0 ml_ of a 1.0 M solution in THF) and boron trifluoride diethyl etherate (0.8 ml_, 6.0 mmol). The reaction is allowed to warm to ambient temperature overnight, and then quenched by pouring into a mixture of ice and solid NaHCO3. Following extraction with EtOAc, the organic layer is washed with brine and dried over Na2SO4. Removal of solvent affords the product as a colorless oil: MS (M+NH4)+ = 204. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With thionyl chloride; at 80℃; for 3h; | A solution of (3-methanesulfonyl) phenyl methanol (0.21 g, 1.1 mmol) in thionyl chloride (3 ML) was heated at 80C for 3 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure to provide 1-CHLOROMETHYL-3- methanesulfonylbenzene as a yellow oil (0.23 g, 95%) : 1H NMR (300 MHz, CDCl3) 8 7.98 (s, 1H), 7.90 (d, J = 8 Hz, 1H), 7.70 (d, J = 8 Hz, 1H), 7.59 (t, J = 8 Hz, 1H), 4.65 (s, 2H), 3.08 (s, 3H). |
77% | With tetrachloromethane; triphenylphosphine; In tetrahydrofuran; at 20 - 75℃; | Triphenylphosphine (7.5 g, 29 mmol), carbon tetrachloride (11.0 ml_, 114 mmol) and tetrahydrofuran (18 ml_) were combined and stirred at room temperature for 10 minutes. A suspension of <strong>[220798-39-0](3-methanesulfonyl-phenyl)-methanol</strong> (2.68 g, 14.3 mmol) in 18 ml_ tetrahydrofuran was added, then the reaction mixture was heated at 75 C for 3 hours. The reaction mixture was cooled to room temperature, then partitioned between ethyl acetate and water. The organic phase was dried over MgSO4, filtered, and concentrated to give the crude product as an oily solid. A solution of this crude product and dichloromethane was evaporated over silica gel, and the resulting silica gel supported crude product was loaded onto an Analogix SuperFlash column. Flash chromatography (15% - 35% ethyl acetate in hexanes) afforded 2.26 g (77%) of 3-(methanesulfonyl)benzyl chloride as a white solid. 1H NMR (300 MHz, DMSO- Cf6) delta ppm 8.01 (s, 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.81 (d, J = 7.8 Hz, 1 H), 7.68 (t, J = 7.8 Hz, 1 H), 4.90 (s, 2 H), 3.24 (s, 3 H). HRMS (El+) cald. for C8H9CIO2S [M+] 204.0012, obsd. 204.0012. |
With methanesulfonyl chloride; triethylamine; In dichloromethane; at 20 - 50℃; for 4h; | 0.267 ml (3.45 mmol) METHANESULPHONYL-CHLORIDE is added to o a solution of 584 mg (3.14 mmol) (3-METHANESULPHONYL-PHENYL)-METHANOL and 0.66 ml (4.71 mmol) triethylamine in 6 ml dichloromethane. This reaction mixture is stirred at room tem- perature for 1 h and at 50 C FOR additional 3 h. The reaction mixture is then poured into water and extracted twice with dichloromethane. The combined organic layers are washed with water and brine, dried, filtered and concentrated in vacuo to afford the title compound, which is used in the next step without further purification. 'H-NMR (300 MHz, DMSO): 7.98 (broad s, 1H), 7. 86 (d, 1H), 7.77 (d, 2H), 7.64 (t, 1H), 4. 86 (s, 2H), 3.21 (s, 3H). |
With methanesulfonyl chloride; triethylamine; In dichloromethane; for 16h; | Borane solution (1M in THF) was added dropwise to a stirred mixture of 3-methylsulfonyl)benzoic acid (400 mg, 2.00 mmol) in anhydrous THF (2 ml) at 0 C. The resulting mixture was then allowed to warm to room temperature and stirred for 3 h. The reaction mixture quenched with water/1 M HCl (aq.), extracted with ethyl acetate (3 times), the combined organic extracts dried (sodium sulfate) and concentrated in vacuo to give crude <strong>[220798-39-0](3-(methylsulphonyl)phenyl)methanol</strong> as an oil which was used in the next step without further purification. The alcohol was dissolved in dichloromethane (6 ml) and triethylamine (0.418 mL, 3.0 mmol). Methanesulfonylchloride (first batch (0.186 mL, 2.4 mmol) was then added, followed by a second batch (0.039 mL, 0.5 mmol) and the resulting mixture was stirred for 16 h. 1 N HCl solution (aq.) was then added and the reaction mixture was extracted with diethyl ether (3 times), the combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by column chromatography eluting using a gradient (petroleum ether 40/60/ethyl acetate 1:0 v/v 0:1) to afford 212 mg (52% over 2 steps) of the title compound as an oil. 1H NMR (CDCl3): 7.98 (1H, s), 7.91 (1H, d, J 7.8), 7.70 (1H, d, J 7.8), 7.59 (1H, t, J 7.8), 4.65 (2H, s), 3.08 (s, 3H). | |
With methanesulfonyl chloride; triethylamine; In dichloromethane; at 0 - 26℃; for 16h; | To a cold (0 C) solution of Intermediate AY (2g, 10.75 mmol) and triethylamine (2.26 mL, 16.12 mmol) in dichloromethane (25 mL) was added slowly methanesulfonyl chloride (1.08 mL, 13.85 mmol) over 5 minutes. After the addition was complete, the reaction mixture was allowed to reach room temperature and stirred for 16 hours. The reaction mixture was quenched with cold water (10 mL), diluted with dichloromethane (20 mL), washed with cold water (2 chi 50 mL) and brine (20 mL), dried over anhydrous Na2S04, and the solvent was removed to afford the crude Intermediate AZ. This material was purified by column chromatography (silica gel 100-200 mesh) using 10% ethyl acetate in petroleum ether as the eluent to afford the product (1.6g, 73%) as a pale yellow oil. NMR (CDC13): delta 7.98 (s, 1H), 7.91 (d, J = 7.80 Hz; 1H), 7.70 (d, J= 7.80 Hz, 1H), 7.59 (t, J= 7.80 Hz; 1H), 4.65 (s, 2H), 3.07 (s, 3H). Mass (M+H): 205.0. | |
With thionyl chloride; In dichloromethane; for 2h; | A suspension of <strong>[220798-39-0](3-(methylsulfonyl)phenyl)methanol</strong> (0.106 g, 0.569 mmol) in dry dichloromethane (3.0 mL) was treated with thionyl chloride (0.249 mL, 3.42 mmol) and the mixture was stirred for 2 hours, during which time all solids dissolved. The reaction was concentrated under reduced pressure and the residue was dried twice from dichloromethane. The residue was used immediately in the following experiment. 1H NMR (400 MHz, CDCl3) delta: 8.07-7.88 (m, 2H), 7.77-7.54 (m, 2H), 5.22-4.99 (m, 1H), 4.66 (s, 1H), 3.10-3.06 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; In ethanol; at 20℃; for 1h; | NaBH4 is added to a solution of 750 mg (4.08 mmol) 3-methanesulphonyl-benz- aldehyde in 20 ml ethanol (see P. L. ORNSTEIN, T. J. Bleisch, M. B. Arnold, R. A. Wright, B. G. Johnson, J. P. Tizzano, D. R. Helton, M. J. Kallman, D. D. SCHOEPP, M. Herin, J MED. Chem. 1998, 41 (3), 358-378 or B. Eistert, W. Schade, H. Selzer, Ber. 1964, 97 (5), 1470-81). The reaction mixture is stirred at room temperature for 1 h. The reaction mixture is poured into water and extracted three times with ethyl acetate. The combined organic layers are washed with water and brine, dried, filtered and concentrated in vacuo to afford the title compound, used in the next step without further purification. H-NMR (300 MHz, DMSO): 7.85 (broad s, 1H), 7.78 (d, 1H), 7.62 (d, 2H), 7.59 (t, 1H), 5.45 (t, 3H), 4.58 (d, 2H), 3.19 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In tetrahydrofuran; | To a solution of methyl 3-methylsulfonylbenzoate (4.4 g, 20.3 mmol) in anhydrous THF (100 mL) was added lithium aluminum hydride (7 mL, 1.0 M solution in THF) via syringe at 0 C. After stirring for 2 hours at room temperature, the mixture was diluted with water, and extracted with diethyl ether. The combined organic extracts were dried (MgSO4), and concentrated to give 3-methylsulfonyl benzyl alcohol (3.5 g, 93%). 1H NMR (CDCl3) delta: 3.02 (s, 3H), 4.68 (s, 2H), 7.47 (t, 1H), 7.57 (d, 1H), 7.75 (d, 1H), 7.89 (s, 1H). |
92% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 1h; | e) Compound 8.4 can also be prepared according to Scheme 7B and the procedure below. [0282] SCHEME 7B [0283] A mixture of 8. 5 (1.0 mmoL), methyl iodide (1.2 mmoL) and potassium carbonate (2 mmoL) in 20 mL of acetone was heated at 50C for 3 hours. The solvent of the reaction mixture was removed under reduced pressure. The residue was partitioned between EtOAc and water. The aqueous solution was extracted with EtOAc, and combined organic solution was washed with brine, dried over Na2S04, filtered, concentrated. The crude product as a white solid (yield 98%) was used for next step without purification. To a solution of the compound (1 mmoL) made above in 4 mL of THF at 0 C was added LiAlH4 (1. 1 mmoL) slowly. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction was added consecutively with water, 15% aqueous NaOH and water with strong stirring. The filtration and evaporation of filtrate provided the crude product 8. 6 (yield 92%). No purification was needed. 1H NMR (400 MHz, CDC13) 6 3.05 (s, 3 H), 4.75 (s, 2 H), 7.53 (t, J=7. 58 Hz, 1 H), 7.62 (d, J=7. 34 Hz, 1 H), 7. 81 (d, J=7. 83 Hz, 1 H), 7.93 (s, 1 H). |
82% | With sodium tetrahydroborate; calcium chloride; In tetrahydrofuran; ethanol; at 20℃; for 1.5h; | To a stirring solution of methyl 3-(methylsulfonyl)benzoate (950 mg, 4.43 mmol) in ethanol (20 mL) and THF ( lOmL) at - 10 C was added calcium chloride (492 mg, 4.43 mmol), followed by sodium borohydride (336 mg, 8.87 mmol). The resulting mixture was then stirred at rt for 30 mins. Tic after this time showed very low conversion. A further amount of NaBH4 (336 mg, 8.87 mmol) was added and the mixture was stirred at rt for further 1 hour. The reaction mixture was poured into sat. aq. NaHC03 (30 mL). The product was extracted with ethyl acetate (50 mL x 5) and the combined organics was dried over Na2S04 and concentrated in vacuo to afford (3-(methylsulfonyl)phenyl)methanol (800 mg, 82%) as a light yellow oil. NMR (300 MHz, CDCI3) delta ppm: 7.98 (s, 1H), 7.88 (dt, ,/ = 7.6, 1.6 Hz, 1H), 7.68 (d, J = 8. 1 Hz, 1 H), 7.59 (dd, ./ = 7.7 Hz, l H), 4.83 (s, 2H), 3.08 (s, 3H). |
64% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 1.08333h;Inert atmosphere; | To a solution of 122A (0.32 g, 1.5 mmol) in THF (7.5 mL) at 0 C under argon, was added LAH (2.25 mL, 2.25 mmol) portion-wise over a period of 5 mm. The reaction was stirred at rt for 1 h, and then was sequentially quenched slowly with water (0.1 mL), 15% NaOH (0.1 mL) and water (0.3 mL). The resulting mixture was stirred atrt for 1 h. The solids were removed by filtration through CELITE, and the filtrate was concentrated. The crude product was purified by silica gel chromatography to provide 122B (0.18 g, 0.96 mmol, 64%) as a colorless oil. MS(ESI) m/z 187.1 (M+H)t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h; | A solution of [3-(methylsulfonyl) phenyl] methanol (680 mg, 3.66 MMOL) IN anhydrous CH2CI2 (20 mL) was treated with PCC (1.03 g, 4.75 mmol) at room temperature for 2 hours. The solvent was removed and the residue was purified by flash column chromatography (20-60% EtOAc in hexanes) to give the product (500 mg, 74% YIELD). H NMR (300 MHz, CDC13) 5 : 3.13 (s, 3 H), 7.77-7. 82 (m, 1 H), 8.18-8. 24 (m, 2 H), 8.46-8. 48 (m, 1 H), 10.12 (s, 1 H). |
72% | With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide; In dichloromethane; at 20℃; for 1h;Molecular sieve; | Solid tetrapropylammonium perruthenate ("TPAP", 0.05 mmol) was added in one portion to a stirred mixture of compound 8. 6 (1 mmoL), 4- methylmorpholine N-oxide ("NMO" ; 1.5 mmoL) and powdered 4A molecular sieve (equal weight to that of NMO) in 5 mL of DCM at room temperature under N2. The reaction mixture was stirred at room temperature. for 1 hour, and then filtered through a short pad of silica gel, eluting with mixture of DCM and AcOEt (1: 1). The filtrate was concentrated and the residue was purified with chromatography (Si02, AcOEt/hexane 2: 1) to afford compound 8.7 (yield 72%). 1H NMR (400 MHz, CDC13) 8 3.14 (s, 3 H), 7.81 (t, J=7. 58 Hz, 1 H), 8.21 (t, J=9. 05 Hz, 2 H), 8.46 (s, 1 H), 10.12 (s, 1 H) ppm. |
To a solution of oxalyl chloride (1.05 mL, 12 mmol) in DCM (15 mL) at -78C is added a solution of DMSO (1.9 mL, 26.6 mmol) in DCM (15 mL) over 5 minutes. The reaction mixture is stirred for 20 minutes, then a solution of <strong>[220798-39-0](3-methanesulfonyl-phenyl)-methanol</strong> (0.992 g, 5.33 mmol) in DCM (20 mL) is added over a 5 minute period. The reaction mixture is stirred for 15 minutes then Et3N (3.78 mL, 27.2 mmol) is added over a 5 minute period. The ice bath is removed and water (30 mL) is added at room temperature. The reaction mixture is stirred for 10 minutes, then the organic layer is isolated, dried over MgSO4 and EPO <DP n="34"/>filtered. The solvent is removed under reduced pressure to yield 3-methanesulfonyl- benzaldehyde as a pale orange solid; [M-H]" 183. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium borohydride; In tetrahydrofuran; water; | Reference Example 13 3-Methanesulfonylbenzyl alcohol Ethyl 3-methanesulfonylbenzoate (420 mg) was dissolved in 4 ml of tetrahydrofuran, 120 mg of lithium borohydride was added to the solution, and the mixture was heated under reflux for 20 hours under an argon atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 283 mg of 3-methanesulfonylbenzyl alcohol. 1H-NMR(CDCl3) delta ppm: 1.91 (1H, t, J=5.8Hz), 3.07 (3H, s), 4.82 (2H, d, J=5.8Hz), 7.57 (1H, t, J=7.7Hz), 7.67 (1H, d, J=7.7Hz), 7.87 (1H, d, J=7.7Hz), 7.97 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; | To a 0 C solution of (3-methanesulfanyl-phenyl)-methanol (4.57 g, 30 mmol) in dichloromethane (100 ml_) was added m-chloroperoxybenzoic acid (16 g, 93 mmol), in portions over the course of 1 hour. The reaction mixture was allowed to warm to room temperature, then stirred for 24 hours. The reaction mixture was washed with a saturated aqueous solution of sodium sulfite followed by a saturated aqueous solution of sodium bicarbonate. The organic phase was dried over Na2SO4, filtered, and evaporated. Flash chromatography (Analogix SuperFlash column, 35% - 50% ethyl acetate in hexanes) gave 2.68 g (49% over three steps) of (3-methanesulfonyl- phenyl)-methanol as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 20 - 50℃;Inert atmosphere; | (13B) Ethyl 3-ethoxy-3-(4-[3-(methylsulfonyl)benzyl]oxy}phenyl)propionateEthyl 3-ethoxy-3-(4-hydroxyphenyl)propionate (100 mg, 0.420 mmol) produced in Example 1 (1C) and <strong>[220798-39-0][3-(methylsulfonyl)phenyl]methanol</strong> (117 mg, 0.630 mmol) produced in (13A) were dissolved in tetrahydrofuran (10 mL), and triphenylphosphine (178 mg, 0.680 mmol) and a 40% diethyl azodicarboxylate toluene solution (309 muL, 0.680 mmol) were added thereto at room temperature, and then, the resulting mixture was stirred under a nitrogen atmosphere at 50 C. for 4 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 95:5 (v/v)), whereby the objective title compound was obtained as a white solid (199 mg, yield: 99%).1H NMR (CDCl3, 400 MHz): delta1.15 (3H, t, J=7.0 Hz), 1.23 (3H, t, J=7.4 Hz), 2.57 (1H, dd, J=5.1, 15.3 Hz), 2.81 (1H, dd, J=9.0, 15.3 Hz), 3.08 (3H, s), 3.30-3.40 (2H, m), 4.23 (2H, q, J=7.3 Hz), 4.71 (1H, dd, J=5.1, 9.0 Hz), 5.14 (2H, s), 6.96 (2H, d, J=9.0 Hz), 7.29 (2H, d, J=8.6 Hz), 7.61 (1H, t, J=7.9 Hz), 7.74 (1H, d, J=8.2 Hz), 7.92 (1H, d, J=8.2 Hz), 8.04 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 15℃; for 14h; | To a solution of 35 (1 .03 g, 5.52 mmol) in DCM (10 mL) were added A/-Boo(S)-valine (1 .00 g,4.60 mmol), DCC (1 .42 g, 6.90 mmol) and DMAP (56.2 mg , 0.460 mmol). The mixture was stirred at 15 C for 14 h. The reaction mixture was filtered and concentrated under reduced pressure (40 C) to give a residue. The residue was purified via column chromatography (Si02, petroleum ether/ethyl acetate = 2: 1) to give 36 (1 .20 g , 68%) was obtained as a yellow oil. |
Tags: 220798-39-0 synthesis path| 220798-39-0 SDS| 220798-39-0 COA| 220798-39-0 purity| 220798-39-0 application| 220798-39-0 NMR| 220798-39-0 COA| 220798-39-0 structure
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