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HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
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Structure of 627-27-0 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] Journal of Organic Chemistry, 1989, vol. 54, # 11, p. 2748 - 2751
2
[ 50-00-0 ]
[ 627-27-0 ]
[ 1768-64-5 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1956, p. 824
[2] Chemische Berichte, 1955, vol. 88, p. 1053,1059
3
[ 7647-01-0 ]
[ 50-00-0 ]
[ 627-27-0 ]
[ 1768-64-5 ]
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 1053,1059
4
[ 627-27-0 ]
[ 19311-37-6 ]
[ 87018-30-2 ]
Reference：
[1] Russian Chemical Bulletin, 2012, vol. 61, # 2, p. 459 - 463[2] Izv. Akad. Nauk, Ser. Khim., 2012, # 2, p. 456 - 460,5
5
[ 627-27-0 ]
[ 19311-37-6 ]
Reference：
[1] Russian Chemical Bulletin, 2012, vol. 61, # 2, p. 459 - 463[2] Izv. Akad. Nauk, Ser. Khim., 2012, # 2, p. 456 - 460,5
[3] Journal of Organic Chemistry, 1996, vol. 61, # 3, p. 962 - 968
6
[ 627-27-0 ]
[ 453-20-3 ]
Reference：
[1] Chemical Communications, 1998, # 4, p. 463 - 464
[2] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[3] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
[4] Journal of Catalysis, 1999, vol. 182, # 2, p. 349 - 356
7
[ 627-27-0 ]
[ 453-20-3 ]
[ 3068-00-6 ]
Reference：
[1] Chemical Communications, 1998, # 4, p. 463 - 464
8
[ 1191-99-7 ]
[ 453-20-3 ]
[ 110-63-4 ]
[ 627-27-0 ]
[ 18826-95-4 ]
Reference：
[1] Journal of Organic Chemistry, 1985, vol. 50, # 10, p. 1582 - 1589
9
[ 110-88-3 ]
[ 627-27-0 ]
[ 2081-44-9 ]
Yield
Reaction Conditions
Operation in experiment
84%
Stage #1: at 80℃; for 4 h; Stage #2: at 64℃;
The same reaction as in Example 2 was carried out except for changing methanol to isopropylalcohol in Example 2. As a result, 32.1 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 84percent).
81%
Stage #1: at 80℃; for 4 - 12.5 h; Stage #2: at 20 - 64℃;
In a glass flask having an inner volume of 2 liters and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device was charged 600 ml of 98percent by weight formic acid, and the mixture was heated to 80°C. Thereafter, a solution containing 300 g (4.16 mol) of 3-buten-1-ol and 149.9 g (1.66 mol) trioxane dissolved in 600 ml of 98percent by weight formic acid was gradually added dropwise to the above mixture over 4.5 hours, and under nitrogen atmosphere, the mixture was subjected to cyclization reaction at the same temperature for 8 hours. Then, after cooling the reaction mixture to room temperature, 5.4 g (56 mmol) of methanesulfonic acids and 600 ml of ethanol were added to the mixture, and the resulting mixture was heated up to 64°C under normal pressure, whereby solvolysis was carried out while removing by-producing ethyl formate. Moreover, after this operation was repeated three times, the reaction mixture was distilled under reduced pressure (85 to 87°C, 173Pa) to obtain 347 g of tetrahydropyran-4-ol (Isolation yield based on 3-buten-1-ol: 81.6percent) as a colorless liquid with a purity of 99.2percent (areal percentage according to gas chromatography). Example 3 (Synthesis of tetrahydropyran-4-ol) The same reaction as in Example 2 was carried out except for changing methanol to ethanol in Example 2. As a result, 30.9 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 81percent). Example 5 (Synthesis of tetrahydropyran-4-ol) In a glass flask having an inner volume of 500 ml and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device were charged 10.0 g (139 mmol) of 3-buten-1-ol, 5.0 g (56 mmol) of trioxane and 40 ml of 98percent by weight formic acid, the mixture was subjected to cyclization reaction under nitrogen atmosphere at 80°C for 4 hours. Then, 0.2 g (2 mmol) of methanesulfonic acid and 50 ml of ethanol were added to the mixture and the resulting mixture was heated up to 64°C, whereby solvolysis was carried out while removing by-producing ethyl formate. Moreover, after the operation was repeated, when the reaction mixture was analyzed by gas chromatography (internal standard method), 13.1 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 92percent).
79%
Stage #1: at 80℃; for 4 h; Stage #2: at 64℃;
In a glass flask having an inner volume of 500 ml and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device were charged 27.0 g (374 mmol) of 3-buten-1-ol, 13.5 g (150 mmol) of trioxane and 133 ml of 98percent by weight formic acid, and the mixture was subjected to cyclization under nitrogen atmosphere at 80°C for 4 hours. Then, formic acid was distilled off from the reaction mixture under reduced pressure, 1 g (10 mmol) of methanesulfonic acid and 200 ml of methanol were added to the residue, and the resulting mixture was heated up to 64°C under normal pressure, whereby solvolysis was carried out while removing by-producing methyl formate. Moreover, after this operation was repeated, when the reaction mixture was analyzed by gas chromatography (internal standard method), 30.2 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 79percent).
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 1053,1059
15
[ 50-00-0 ]
[ 627-27-0 ]
[ 7664-93-9 ]
[ 7732-18-5 ]
[ 2081-44-9 ]
[ 5684-93-5 ]
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 1053,1059
[2] Zhurnal Obshchei Khimii, 1955, vol. 25, p. 133,135; engl. Ausg. S. 119, 121
16
[ 50-00-0 ]
[ 627-27-0 ]
[ 25637-16-5 ]
Reference：
[1] Chemische Berichte, 1955, vol. 88, p. 1053,1059
17
[ 627-27-0 ]
[ 5162-44-7 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 3, p. 928 - 935
[2] Organic Letters, 2017, vol. 19, # 9, p. 2310 - 2313
[3] Journal of the Chemical Society, 1934, p. 1998
[4] Chemische Berichte, 1930, vol. 63, p. 1991
[5] Bulletin de la Societe Chimique de France, 1965, p. 1550 - 1555
[6] Journal of Organic Chemistry, 1974, vol. 39, p. 3102 - 3107
[7] Canadian Journal of Chemistry, 1970, vol. 48, p. 3953 - 3957
[8] Journal of Organic Chemistry, 1972, vol. 37, p. 152 - 154
[9] Journal of Organometallic Chemistry, 1985, vol. 288, p. 349 - 358
[10] Journal of Chemical Research, Miniprint, 1997, # 1, p. 228 - 240
[11] Organic Letters, 2013, vol. 15, # 10, p. 2374 - 2377
18
[ 627-27-0 ]
[ 5162-44-7 ]
[ 107-80-2 ]
Reference：
[1] Monatshefte fuer Chemie, 1914, vol. 35, p. 1509
[2] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[3] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
[4] Monatshefte fuer Chemie, 1914, vol. 35, p. 1509
[5] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[6] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
[7] Monatshefte fuer Chemie, 1914, vol. 35, p. 1509
[8] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[9] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
19
[ 50-00-0 ]
[ 627-27-0 ]
[ 5162-44-7 ]
Reference：
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 9, p. 802 - 805
20
[ 627-27-0 ]
[ 10035-10-6 ]
[ 5162-44-7 ]
[ 107-80-2 ]
Reference：
[1] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
[3] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[4] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
21
[ 627-27-0 ]
[ 7664-93-9 ]
[ 10035-10-6 ]
[ 5162-44-7 ]
[ 4784-77-4 ]
Reference：
[1] Journal of the Chemical Society, 1934, p. 1998
[2] Journal of the Chemical Society, 1936, p. 264
22
[ 627-27-0 ]
[ 7789-60-8 ]
[ 5162-44-7 ]
[ 107-80-2 ]
Reference：
[1] Annales de Chimie (Cachan, France), 1911, vol. <8>24, p. 330[2] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1910, vol. 150, p. 1056
23
[ 58390-09-3 ]
[ 109-99-9 ]
[ 627-27-0 ]
[ 4696-30-4 ]
[ 13330-96-6 ]
[ 33962-95-7 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1983, vol. 48, # l, p. 1734 - 1744
24
[ 76387-45-6 ]
[ 627-27-0 ]
[ 2516-33-8 ]
[ 2919-23-5 ]
Reference：
[1] Journal of the American Chemical Society, 1981, vol. 103, # 2, p. 442 - 445
25
[ 70458-21-8 ]
[ 627-27-0 ]
[ 2516-33-8 ]
[ 70458-29-6 ]
[ 70458-27-4 ]
[ 70458-28-5 ]
[ 2919-23-5 ]
Reference：
[1] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3722 - 3723
[2] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3722 - 3723
[3] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3722 - 3723
[4] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3722 - 3723
With dmap; triethylamine; In dichloromethane; at 0℃;Inert atmosphere;
General procedure: The unsaturated alcohol (1.00 mmol) was dissolved in CH2Cl2 (10 mL), and a small amount ofN,N-dimethylaminopyridine was added. The solution was cooled to 0 C, and triethylamine (1.20mmol) was added. Then, 2-methyl<strong>[14418-84-9]allylsulfonyl chloride</strong> (0.186 g, 1.20 mmol) was slowly added withcooling and stirring. The resultant solution was stirred at 0 C until complete conversion of the alcoholsubstrate (1-2 h). In order to remove triethylammonium hydrochloride, the mixture was filteredthrough a plug of silica gel, which was eluted with Et2O. After removal of the volatiles under reducedpressure, the crude product was purified by flash chromatography on silica gel to give the sulfonates2b and 2c
90%
With TEA; In dichloromethane; at -20 - 20℃; for 4.5h;
General procedure: To a stirredsolution of the unsaturated alcohol (2a,b) (1.0 equiv.) and dry TEA (1.5 equiv.) in CH2Cl2 at low temperature (-20 oC) was added ally sulfonyl chloride (1.2 equiv.) in CH2Cl2 drop by drop. The reaction mixture was left to stirunder this temperature for 4 h then left to stir for 0.5 h at room temperature. Pentane was then added andthe mixture was filtered through Celite. The filtrate was concentrated under reduced pressure and the crudresidue was purified by flash chromatography.
With sodium hydride; In 1,4-dioxane; at 0 - 100℃; for 62h;
EXAMPLE 1C 6-(3-butenyloxy)-2-pyrazinamine A suspension of NaH (60percent, 618 mg, 15.45 mmol) in dioxane (30 mL) at 0° C. was treated with 3-buten-1-ol (1.33 mL, 15.45 mmol), stirred for 2 hours, treated with <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (1 g, 7.72 mmol), stirred at 100° C. for 2.5 days, cooled to room temperature, and diluted with ethyl acetate. The mixture was washed with water, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography eluding with hexanes/ethyl acetate (2:1) to provide the desired product (390 mg, 31 percent). MS (DCI/NH3) m/z 166.12 (M+H)+; 1H NMR (500 MHz, benzene-d6) delta 2.66 (m, 2H), 4.42 (t, J=6.87 Hz, 2H), 5.24 (dd, J=10.22, 1.98 Hz, 1H), 5.30 (m, 1H), 6.04 (m, 1H), 7.64 (s, 1H), 7.65 (s, 1H).
31%
Example 1C 6-(3-butenyloxy)-2-pyrazinamine A suspension of NaH (60percent, 618 mg, 15.45 mmol) in dioxane (30 mL) at 0° C. was treated with 3-buten-1-ol (1.33 mL, 15.45 mmol), stirred for 2 hours, treated with <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (1 g, 7.72 mmol), stirred at 100° C. for 2.5 days, cooled to room temperature, and diluted with ethyl acetate. The mixture was washed with water, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography eluding with hexanes/ethyl acetate (2:1) to provide the desired product (390 mg, 31percent). MS (DCI/NH3) m/z 166.12 (M+H)+; 1H NMR (500 MHz, benzene-d6) delta 2.66 (m, 2H), 4.42 (t, J=6.87 Hz, 2H), 5.24 (dd, J=10.22, 1.98 Hz, 1H), 5.30 (m, 1H), 6.04 (m, 1H), 7.64 (s, 1H), 7.65 (s, 1H).
With toluene-4-sulfonic acid; In hexane; for 3h;Heating / reflux;
Synthesis of Compound 13; p-Toluenesulfonic acid monohydrate (4.0 g) was added to a mixture of chlorodifluoroacetic acid (12) (58.0 g), 3-buten-1-ol (30.5 g) and hexane (100 ml), and the resultant mixture was heated under reflux for 3 hours, while conducting dehydration. After the reaction mixture was extracted with hexane/aqueous sodium bicarbonate solution, the organic layer was washed with water and an aqueous saturated sodium chloride solution, and then dried over magnesium sulfate. Concentration of the solvent, and distillation under reduced pressure gave Compound 13 (66.0 g, 85%). 1H NMR (400 MHz; solvent, CDCl3; standard, TMS) 5.83-5.73 (m, 1H), 5.19 (s, 1H), 5.18-5.13 (m, 1H), 4.40 (t, J=6.3, 2H), 2.50 (q, J=6.3, 2H)
With potassium hydroxide; tetrabutylammomium bromide; In dichloromethane; water; at 20℃; for 96h;
6-Bromocapronitrile (1.19ml, 9.00mmol) and 3-buten-1-ol (946ul, H .Ommol) were added to a stirred solution of potassium hydroxide (6.16g, 110mmol) and tetra-butylammonium bromide (434mg, 1.35mmol) in water (6ml) and dichloromethane (2ml). The reaction was stirred at room temperature for 4 days and then washed with diethyl ether (2x50ml). The combined organics were washed with water (3x30ml), dried (magnesium sulphate) and the solvent removed in vacuo to furnish the title compound as a colourless oil, 1.48g. LRMS: m/z 168 [M+H]+.
Sodium hydride (2.3 g) was added to a tetrahydrofuran (200 mL) solution of 3-buten-1-ol (5.2 mL) under ice cooling, and the reaction mixture was then stirred at the same temperature for 30 minutes. The compound (14.8 g) prepared in <Step 6> of Example 235 and tetra-n-butylammonium iodide (1.5 g) were added thereto, and the reaction mixture was stirred at room temperature for 12 hours. Water was added to the reaction mixture, and the reaction mixture was then extracted with ethyl acetate. The organic layer was washed with a saturated brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluate; n-hexane:ethyl acetate 100:0 to 95:5). The title compound (13.9 g) was obtained as yellow oil.
Sodium hydride (2.3 g) was added to a tetrahydrofuran (200 mL) solution of 3-buten-1-ol (5.2 mL) under ice cooling, and the reaction mixture was then stirred at the same temperature for 30 minutes. The compound (14.8 g) prepared in <Step 6> of Example 235 and tetra-n-butylammonium iodide (1.5 g) were added thereto, and the reaction mixture was stirred at room temperature for 12 hours. Water was added to the reaction mixture, and the reaction mixture was then extracted with ethyl acetate. The organic layer was washed with a saturated brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluate; n-hexane:ethyl acetate = 100:0 to 95:5). The title compound (13.9 g) was obtained as yellow oil.
3-butenyl 5-aminolevulinate hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
Example 2 Preparation of 3-Butenyl 5-Aminolevulinate Hydrochloride To 1 ml of thionyl chloride (SOCl2) were added 3 drops of N,N-dimethylformamide (DMF) with stirring. Following the addition of <strong>[5451-09-2]5-aminolevulinic acid hydrochloride</strong> (ALA.HCl, 200 mg, 1.19 mmol), the solution was stirred for 12 hours at room temperature. Concentration in a vacuum was conducted before the addition of 3-butenol. Then, the reaction mixture was stirred for 1.5 hours at room temperature, followed by purification by silica gel chromatography to afford 3-butenyl 5-aminolevulinate hydrochloride at a yield of 77%. 1H NMR (300 MHz, DMSO-d6): delta8.24 (s, 3H), 5.80-5.74 (m, 1H), 5.16-5.04 (m, 2H), 4.06 (t, J=6.63 Hz, 2H), 2.80 (t, J=6.63 Hz, 2H), 2.52 (t, J=6.6 Hz, 2H), 2.33 (q, J=6.54, 2H); 13C NMR (75 MHz, DMSO-d6): delta 172.07, 152.64, 143.20, 134.43, 117.07, 62.88, 32.52, 31.90, 28.91
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0℃; for 1h;Reflux;
Step b: 2,6-dibromo-3-but-3-enoxy-pyridine. To a stirred mixture of <strong>[6602-33-1]2,6-dibromopyridin-3-ol</strong> (47.3 g, 0.188 mol) and but-3-en-1 -ol (13.8 g, 0.191 mol) in anhydrous THF (200 mL) at 0 C was added PPh3 (59.4 g, 0.226 mol), followed by diisopropylazo dicarboxylate (DIAD, 41.77 g, 0.207 mol). The mixture was heated at reflux for 1 hour and then concentrated in vacuo to give a dark brown oil. The oil was dissolved in Ethyl acetate, washed with saturated NaHC03 solution and brine, dried with Na2S04, and concentrated in vacuo. Petroleum (300 mL) was added to the crude product mixture. The white solid was removed by filtration, and the filtrate was purified by silica gel chromatography (petroleum / Ethyl acetate, 30/1 ) to afford compound the title compound as oil (49 g, 85%). 1H NMR (400Mz, DMSO-d6): delta : 2.62-2.59 (m, 2H);4.07-4.03 (t, J=6, 2H);5.22-5.1 1 (m, 1 H);5.96-5.83 (m, 1 H);7.01 (d, J=7.2),;7.33 (d, J=9.3, 1 H).
70.6%
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0℃;Reflux;
Step 2. Synthesis of2,6-dibromo-3-(but-3-enyloxy)pyridine (40):39 reflux 24h 40 To a stirred mixture of <strong>[6602-33-1]2,6-dibromopyridin-3-ol</strong> (39; 35 g, 138 mmol) and but-3-en- l-ol (12.15 ml, 141 mmol) in anhydrous THF (10 ml) at O ºC was added triphenylphosphine (43.6 g, 166 mmol), followed by diethylazodicarboxylate (23.97 ml, 152 mmol). The mixture was heated at reflux for 1 hour and then concentrated in vacuo to give a dark brown oil. The oil was dissolved in EtOAc, washed with a saturated NaHCtheta3 solution and brine, dried with Na2SO4, and concentrated in vacuo. The crude product mixture was dissolved in dichloromethane. The white solid was removed by filtration, and the filtrate was purified by silica gel chromatography to afford the title compound 40 (3Og, 70.6% yield). MS (ESI) calcd for C9H9Br2NO 305.91, found 305.82[M+H].
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0℃; for 1h;Reflux;
To a stirred mixture of <strong>[6602-33-1]2,6-dibromopyridin-3-ol</strong> (47.3 g, 0.188 mol) and but-3-en-1-ol (13.8 g, 0.191 mol) in anhydrous THF (200 ml) at 0 C was added PPh3 (59.4 g, 0.226 mol), followed by diethyl azodicarboxylate (41.77 g, 0.207 mol). The mixture was heated at reflux for 1 h and then concentrated in vacuo to give a dark brown oil. The oil was dissolved in EtOAc, washed with saturated NaHC03 solution and brine, dried with Na2S04, and concentrated in vacuo. Petroleum (300 ml) was added to the crude product mixture. The white solid was removed by filtration, and the filtrate was purified by silica gel chromatography (petroleum / EtOAc, 30/1) to afford the title compound as an oil. 1H NMR (300Mz, DMSO-d6): delta 7.33 (d, J=9.3, 1H), 7.01 (d, J=7.2), 5.96-5.83 (m, 1H), 5.22- 5.11 (m, 1H), 4.07-4.03 (t, J=6, 2H), 2.62-2.59 (m, 2H).
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 6h;
Step B - Synthesis of Intermediate Compound Int-4b: To a mixture of compound Int-4a (14.5 g, 80 mmol), but-3-en-1-ol (11.5 g, 160 mmol), and Ph3P (31.4 g, 120 mmol) in anhydrous THF (500 mL) cooled to 0 C was added DIAD (24.1 g, 120 mmol) dropwise. After addition, the mixture was allowed to stir at room temperature for 6 hours. The solvent was concentrated in vacuo and the residue obtained waspurified using flash column chromatograpy on silica gel (2/1 petroleum ether/EtOAc) to provide compound Int-4b (12.4 g, 60%) as a yellow oil. ?H NMR (400 MHz, CDC13) 5 8.16-8.23 (m, 1H), 6.97-7.03 (m, 1H), 6.85-6.91 (m, 1H), 5.83-5.91 (m, 1H), 5.13-5.17 (m, 2H), 4.07-4.11 (t, J = 7.6 Hz, 2H), 2.48-2.54 (m, 2H)
60%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 6h;
Step B - Synthesis of Intermediate Compound Int-4b To a mixture of compound Int-4a (14.5 g, 80 mmol), but-3-en-l-ol (1 1.5 g, 160 mmol), and Ph3P (31.4 g, 120 mmol) in anhydrous THF (500 mL) cooled to 0 C was added DIAL) (24.1 g, 120 mmol) dropwise. After addition, the mixture was allowed to stir at room temperature for 6 hours. The solvent was concentrated in vacuo and the residue obtained was purified using flash column chromatograpy on silica gel (2/1 petroleum ether/EtOAc) to provide compound Int-4b (12.4 g, 60%) as a yellow oil. 1H MR (400 MHz, CDC13) delta 8.16-8.23 (m, 1H), 6.97-7.03 (m, 1H), 6.85-6.91 (m, 1H), 5.83-5.91 (m, 1H), 5.13-5.17 (m, 2H), 4.07-4.1 1 (t, J = 7.6 Hz, 2H), 2.48-2.54 (m, 2H).
60%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 6h;
To a mixture of compound Int-4a (14.5 g, 80 mmol), but-3-en-1-ol (11.5 g, 160 mmol), and Ph3P (31.4 g, 120 mmol) in anhydrous THF (500 mL) cooled to 0 C. was added DIAD (24.1 g, 120 mmol) dropwise. After addition, the mixture was allowed to stir at room temperature for 6 hours. The solvent was concentrated in vacuo and the residue obtained was purified using flash column chromatography on silica gel (2/1 petroleum ether/EtOAc) to provide compound Int-4b (12.4 g, 60%) as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 8.16-8.23 (m, 1H), 6.97-7.03 (m, 1H), 6.85-6.91 (m, 1H), 5.83-5.91 (m, 1H), 5.13-5.17 (m, 2H), 4.07-4.11 (t, J=7.6 Hz, 2H), 2.48-2.54 (m, 2H).
With pyridine; osmium(VIII) oxide; water; 4-methylmorpholine N-oxide; In tert-butyl alcohol; for 24h;Reflux; Inert atmosphere;
General procedure: The homoallylic alcohol (13.4 mmol) was taken up in a 250 mL 3-neck round bottomed flask to which were added OsO4 (0.28 mol%), NMO (13.4 mmol) and pyridine (13 M), and heated to a gentle refluxin t-BuOH:H2O (5:1) for 24h. The crude mixture was then washed with Na2SO3 (50 mL) and EtOAc (3 x 100 mL). The solvent was evaporated and the crude residue was purified by column chromatography.
methyl 2-bromo-5-(but-3-en-1-yloxy)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
General procedure: Diisopropyl azodicarboxylate (4.22 mL, 21.69mmol, 1.10 equiv.) was added dropwise to a solution of methyl 3-hydroxybenzoate (3.0g, 19.72 mmol), triphenylphosphine (5.69 g, 21.69 mmol, 1.10 equiv.) and but-3-en-1-ol(1.88 mL, 21.69 mmol, 1.10 equiv.) in anhydrous THF (5.0 mL) at 0 C. The cold bathwas removed and the mixture was stirred at 23 C for 12 hours. Then, the mixture wasevaporated together with silica gel. The desired methyl benzoate was isolated bycolumn chromatography on silica gel (pentane:EtOAc, 25:1), affording 3.77 g (93 %yield) of title compound as colorless oil.
methyl 5-(but-3-en-1-yloxy)-2-methylbenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
General procedure: Diisopropyl azodicarboxylate (4.22 mL, 21.69mmol, 1.10 equiv.) was added dropwise to a solution of methyl 3-hydroxybenzoate (3.0g, 19.72 mmol), triphenylphosphine (5.69 g, 21.69 mmol, 1.10 equiv.) and but-3-en-1-ol(1.88 mL, 21.69 mmol, 1.10 equiv.) in anhydrous THF (5.0 mL) at 0 C. The cold bathwas removed and the mixture was stirred at 23 C for 12 hours. Then, the mixture wasevaporated together with silica gel. The desired methyl benzoate was isolated bycolumn chromatography on silica gel (pentane:EtOAc, 25:1), affording 3.77 g (93 %yield) of title compound as colorless oil.
General procedure: Diisopropyl azodicarboxylate (4.22 mL, 21.69mmol, 1.10 equiv.) was added dropwise to a solution of methyl 3-hydroxybenzoate (3.0g, 19.72 mmol), triphenylphosphine (5.69 g, 21.69 mmol, 1.10 equiv.) and but-3-en-1-ol(1.88 mL, 21.69 mmol, 1.10 equiv.) in anhydrous THF (5.0 mL) at 0 C. The cold bathwas removed and the mixture was stirred at 23 C for 12 hours. Then, the mixture wasevaporated together with silica gel. The desired methyl benzoate was isolated bycolumn chromatography on silica gel (pentane:EtOAc, 25:1), affording 3.77 g (93 %yield) of title compound as colorless oil.
methyl 7-(but-3-en-1-yloxy)benzo[d][1,3]dioxole-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
General procedure: Diisopropyl azodicarboxylate (4.22 mL, 21.69mmol, 1.10 equiv.) was added dropwise to a solution of methyl 3-hydroxybenzoate (3.0g, 19.72 mmol), triphenylphosphine (5.69 g, 21.69 mmol, 1.10 equiv.) and but-3-en-1-ol(1.88 mL, 21.69 mmol, 1.10 equiv.) in anhydrous THF (5.0 mL) at 0 C. The cold bathwas removed and the mixture was stirred at 23 C for 12 hours. Then, the mixture wasevaporated together with silica gel. The desired methyl benzoate was isolated bycolumn chromatography on silica gel (pentane:EtOAc, 25:1), affording 3.77 g (93 %yield) of title compound as colorless oil.
methyl 4-bromo-3-(but-3-en-1-yloxy)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
General procedure: Diisopropyl azodicarboxylate (4.22 mL, 21.69mmol, 1.10 equiv.) was added dropwise to a solution of methyl 3-hydroxybenzoate (3.0g, 19.72 mmol), triphenylphosphine (5.69 g, 21.69 mmol, 1.10 equiv.) and but-3-en-1-ol(1.88 mL, 21.69 mmol, 1.10 equiv.) in anhydrous THF (5.0 mL) at 0 C. The cold bathwas removed and the mixture was stirred at 23 C for 12 hours. Then, the mixture wasevaporated together with silica gel. The desired methyl benzoate was isolated bycolumn chromatography on silica gel (pentane:EtOAc, 25:1), affording 3.77 g (93 %yield) of title compound as colorless oil.
2-(4-methylsulfonylphenyl)tetrahydropyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
Step 1 : 2-(4-Methylsulfonyl-phenyl)-tetrahvdro-pyran-4-ol 4-Methylsulfonyl-benzaldehyde (2 g, 10.86 mmol) was dissolved in DCE (40 mL) and cooled in an ice bath. TFA (16 mL) followed by 3-butenol (1.13 mL, 13.03 mmol) were added and the mixture stirred at RT for 67 h. The mixture was diluted with H20 (100 mL), basified with 6 M NaOH (aq) and extracted with DCM (100 mL). The organic layer was separated and washed with brine, dried (Na2S04) and con- centrated under reduced pressure to get crude. The crude product was dissolved in MeOH (20 mL) and LiOH (1.19 g, 28.40 mmol) was added. The reaction was stirred at RT for 5 h. MeOH was concentrated under reduced pressure and the residue was diluted with DCM (100mL) and washed with water (50 mL), brine (50 mL), dried (Na2S04) and concentrated in vacuo to get crude. The crude compound was triturated with n-hexane (10 mL) and Et20 (10 mL) to give 2-(4-Methylsulfonyl-phenyl)-tetrahydro-pyran-4- ol (1.8 g; 64percent) as pale yellow solid.
2-(3-bromo-4-fluorophenyl)tetrahydropyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
58%
Step 1 : 2-(3-Bromo-4-fluoro-phenylHetrahvdro-pyran-4-ol To a solution of 3-bromo-4-fluorobenzaldehdye (10 g, 49.50 mmol) in DCE(200 mL) was added 3-buten- 1 -ol (5.34 g, 74.25 mmol) and TFA (80 mL) and the RM was stirred for 2 d at RT. The RM was quenched with ice-water (200 mL) and basified using 6N NaOH solution to pH=8, the aq layer was extracted with DCM (2x 200 mL). The combined organic layer was washed with H20 (100 mL), brine (100 mL), dried (Na2S04) and concentrated under reduced pressure to get crude (10 g). The crude compound (10 g, 37.17 mmol) was dissolved in MeOH (100 mL), LiOH was added (7.8 g, 42 mmol) and stirred for 5 h at RT. The RM was concentrated under reduced pressure and the residue was diluted with DCM (300 mL). The organic layer was washed with H20 (100 mL), brine (100 mL), dried (Na2S04) and concentrated in vacuo to get crude. The crude was purified by CC (silica gel, 0-30% EtOAc in PE) to obtain 2-(3-Bromo-4- fluoro-phenyl)-tetrahydro-pyran-4-ol (8 g, 58%).
2-(4-chloro-2-methylphenyl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
Step 1 : 2-(4-chloro-2-methylphenyl)tetrahvdro-2H-pyran-4-ol <strong>[40137-29-9]4-chloro-2-methyl-benzaldehyde</strong> (10 g, 64.93 mmol) was dissolved in DCE (200 mL), cooled in an ice bath and TFA (80 mL) followed by 3-butenol (6.76 mL, 77.79 mmol) was added and stirred at RT for 62 h. The mixture was concentrated in vacuo and the residue diluted with water (500 mL), basified with 6M NaOH (aq) and extracted with DCM (800 mL). The organic layer was separated and washed with brine, dried (Na2S04) and concentrated under reduced pressure to get the crude product. The crude product was dissolved in MeOH (125 mL) and LiOH (13.63 g, 324.52 mmol) was added. The reaction was stirred at RT for 5 h. MeOH was concentrated under reduced pressure and the residue was diluted with DCM (200 mL) and washed with water (100 mL), brine (100 mL), dried (Na2S0 ) and concentrated in vacuo to get crude. Purification by CC (silica gel, 0-15% EtOAc in PE) gave 2-(4-chloro-2-methylphenyl)tetrahydro- 2H-pyran-4-ol (7.8 g; 54%) as a thick liquid.
2-(4-chloro-3-methoxyphenyl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
Step 1 : 2-(4-chloromethoxyphenyl) tetrahvdro-2H-pyran-4-ol TFA (48 mL) was added to a stirred solution of 4-chloro-3-methoxy benzaldehyde (6 g, 35.16 mmol) in DCE (120 mL) at 0°C and 3-buten-1 -ol (2.53 g, 35.16 mmol) was added dropwise to the RM at the same temperature and stirred it for 3 d at RT. The RM was diluted with H20 (100 mL) and the aq. layer was basify with 6 N NaOH (pH-10), the aq layer was extracted with DCM (2x100 mL).The combined organic layer was successively washed with H20 (100 mL), brine (100 mL), then dried (Na2S04), filtered and evaporated to give crude. LiOH (7.38 g, 35.16 mmol) was added to a stirred solution of the crude compound in MeOH (120 mL) at RT. The RM was stirred for 16 h at RT. The RM was evaporated to give the residue, the residue was diluted with H20 (150 mL) and extracted with EtOAc (3x100 mL), the combined organic layer was washed with brine (100 ml). ), then dried (Na2S0 ), filtered and evaporated the solvent under vacuo to give crude. Which was purified by CC (silica gel, 25-30percent EtOAc in PE) to give 2-(4-chloromethoxyphenyl) tetrahydro-2H-pyran-4-ol (6 g, 70percent) as a liquid.
2-(2,5-dibromophenyl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
Step 1 : 2-(2,5-dibromophenyl)tetrahvdro-2H-pyran-4-ol 2,5-di bromobenzaldehyde (30 g, 114.5 mmol) was dissolved in DCE (600 mL) and cooled in an ice bath. TFA (240 mL) followed by 3-buten-1-ol (12.36 g, 171.7 mmol) were added and the mixture stirred at RT for 37 h. The mixture was diluted with ice water (500 mL), basified with 6 M NaOH (aq) and extracted with DCM (200 mLx5). Organic layer was separated and washed with brine (500 mL), dried (Na2S0 ) and concentrated under reduced pressure to get crude. The crude product was dissolved in MeOH (200mL) and LiOH H20 (16.7 g, 274 mmol) was added. The reaction was stirred at RT for 16h. MeOH was concentrated under reduced pressure and the residue was diluted with DCM (500 mL) and washed with water (300 mL), brine (200 mL), dried (Na2S04) and concentrated in vacuo to get crude. The crude compound was purified by column chromatography (silica gel, 0-20% EtOAc in PE) to obtain 2-(2,5-di- bromophenyl)tetrahydro-2H-pyran-4-ol (25 g, 65%) as an oil.
2-(2-bromo-4-chlorophenyl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
36%
With sulfuric acid; at 20℃; for 16h;Cooling with ice;
2-(2-bromo-4-chlorophenyl)tetrahvdro-2H-pyran-4-ol Concentrated H2S04 was added drop wise to an ice-cold mixture of 3-buten-1 -ol (6.2 mL, 68.5 mmol, 2.0 eq) and <strong>[84459-33-6]2-bromo-4-chlorobenzaldehyde</strong> (7.5 g, 34.25 mmol, 1.0 eq) and the RM was allowed to warm to RT slowly and stirred for 16 h. Then the RM was poured into ice water, basified with sat. NaHC03 solution and extracted with DCM (2x100 mL), combined organic layer was dried over anhydr. Na2S04, filtered and concentrated under reduced pressure. The crude product was purified by CC to afford 2-(2-bromo-4- chlorophenyl)tetrahydro-2H-pyran-4-ol (3.6 g, 36%) as deep brown liquid.
2-(2-(trifluoromethyl)pyrimidin-5-yl)tetrahydro-2H-pyran-4-yl methanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
In dichloromethane; at 0 - 23℃; for 1.5h;
A solution of <strong>[304693-66-1]2-(trifluoromethyl)pyrimidine-5-carbaldehyde</strong> (860 mg, 4.88 mmol) and but-3-en-1 -01 (0.420 mL, 4.88 mmol) in DCM (5.2 mL) was cooled to 0C. MsOH (3.17 mL, 48.8 mmol) was added dropwiseand the RM was stirred at RT for 90 mm. DCM (30 mL) was added, followed by the careful addition of sat. aq. NaHCO3 (30 mL). The organic layer was washed with sat. aq. NaHCO3 (2x30 mL), dried (Na2SO4) and evaporated under reduced pressure. The product was purified by flash chromatography (silica, gradient heptane/EtOAc, 1:0 to 1:1), to give 1.24 g (78%) of the desired product.
2-(6-(trifluoromethyl)pyridin-3-yl)tetrahydro-2H-pyran-4-yl methanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In dichloromethane; at 23℃; for 4h;Cooling with ice;
Methanesulfonic acid (13.0 mL, 200 mmol) was dropwise added to a solution of 6-(trifluoromethyl)nicotin- aldehyde (3.50 g, 20.0 mmol) and but-3-en-1 -ol (1.72 mL, 20.0 mmol) n DCM (20 mL) while cooling withan icebath. The RM was stirred at RT for 4 h, diluted with DCM, washed with sat. aq. NaHCO3 and separated with a phase separator. The organic layer was further diluted with DCM, washed with sat. aq. NaHCO3 (2x), dried (Na2SO4) and concentrated. Crystallisation (EtOAc/heptane) of the residue gave the product (3.48 g, 54%) as white crystals. The mother liquor was concentrated and crystallisation (EtOAc/Heptane/i-Pr20) of the residue gave another crop of product (1 .73 g, 27%) as white crystals. Thecrystals were combined to give the desired product (5.21 g, 80%).
2-(5-bromo-3-chloropyridin-2-yl)tetrahydro-2H-pyran-4-yl methanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
18 g
In dichloromethane; at 0 - 23℃; for 16h;
Methane sulfonic acid (35.7 ml, 550.45 mmol, 10 eq) was added to a solution of 5-bromo-3-chloro-picolinaldehyde (see Example 88) (12 g, 55.04 mmol, I eq) in DCM (200 ml) at 0C. But-3-en-1-ol (4.5 ml, 55.04 mmol, 1 eq) was added and the mixture stirred for 16 h at RT. The RM was quenched with sat. Na2CO3 solution and extracted with DCM (3 X 150 ml). The organics were washed with water (150 ml) and brine (150 ml), dried (Na2SQ4) and the the solvent was distilled-off under reduced pressure to afford the desired product (18 g).
2-(5-chloropyridin-2-yl)tetrahydro-2H-pyran-4-yl methanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane; at 0 - 15℃; for 3h;
Methanesulfonic acid (20.3g, 212.Ommol) was added to a solution of 5-chloropicolinaldehyde (3g, 21.20 mmol) and 3-buten-1-ol (2.2 g, 31.80 mmol) in DCM (3OmL) at 0C, stirred for 3 h at 0C-i 5C. The RM was quenched into ice water, diluted with DCM (1 5mL) and washed sequentially with sat. aq. NaHCO3 solution (2x5OmL), water (lOOmL), brine (lOOmL), dried (anhydr. Na2504) and concentrated underreduced pressure to get crude 2-(5-chloropyridin-2-yl)tetrahydro-2H-pyran-4-yl methanesulfonate (6.2 g crude) as a brown oil. This was taken to the next step without further purification.
2-(5-(trifluoromethyl)pyridin-2-yl)tetrahydro-2H-pyran-4-yl methanesulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane; at 23℃; for 3h;Cooling with ice;
A solution of <strong>[31224-82-5]5-(trifluoromethyl)picolinaldehyde</strong> (3.82 g, 21.82 mmol) in DCM (20 mL) was prepared, followed by applying an ice/water bath and dropwise addition of methanesulfonic acid (14.1 mL, 218mmol). Subsequently, 3-buten-1-ol (2.25 mL, 26.2 mmol) was added. The RM was stirred at RT for 3 h and poured out in 10% aq. K3P04 (300 mL). Addition of some ice and DCM (300 mL) resulted in a clear two phase system. The phases were separated, the aq. layer was extracted with DCM (50 mL). The combination of organic layers was dried (brine & Na2SO4) and concentrated in vacuo. The residue was dissolved in DCM (5 mL), addition of heptane (200 mL) was followed by evaporation of the DCM in vacuo.Trituration, followed by air-drying provided 5.25 g (59%, purity 80%) of the desired product as an off-white solid.
2-(5-bromo-3-chloropyridin-2-yl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
17%
With sulfuric acid; at 0 - 23℃; for 16h;
Conc. sulfuric acid (5.0 mL) was added to an ice-cold (0C) mixture of <strong>[885168-04-7]5-bromo-3-chloropicolinaldehyde</strong>(5 g, 22.7 mmol, 1 eq) and 3-butene-1-ol (4.1 mL, 45.5 mmol, 2 eq) and the mixture was stirred for 16 h at RT. The reaction mass was poured into crushed ice, neutralized by addition of solid NaHCO3, extracted with EtOAc (2x1 00 mL) and the organic layer was washed with brine (150 ml). Combined organic layer was dried over anhydr. Na2SO4, filtered and the solvent was evaporated under reduced pressure to get crude mass which was then purified by combiflash CC to afford 2-(5-bromo-3-chloropyridin-2-yl)tetra-hydro-2H-pyran-4-ol (1.1 g, 17%) as colorless oil.
2-(5-(trifluoromethyl)pyridin-2-yl)tetrahydro-2H-pyran-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
36%
To a stirred solution of but-3-en-1-ol (1.2 g, 17.1 mmol, 1.0 eq) in DCE (80 mL) and TFA (24 mL, 308 mmol, 18 eq), <strong>[31224-82-5]5-(trifluoromethyl)picolinaldehyde</strong> (3.0 g, 17.1 mmol, 1 eq) was added and the mixture wasstirred for 72 h. After completion of the reaction it was quenched with ice water, basified with NaOH and extracted with DCM. The organic layer was dried over anhydr. Na2SO4, filtered and evaporated under reduced pressure to give yellow oil. The residue was dissolved in MeOH (50 mL) and LiOH (1.2 g, 51.3 mmol, 3.0 eq) was added at RT and the mixture was stirred for 2 h until no evidence of the ester remained. The RM was evaporated to dryness and dissolved in DCM and dried over anhydr. Na2SO4 togive crude product which was further purified by CC to afford 2-(5-(trifluoromethyl)pyridin-2-yl)tetrahydro-2H-pyran-4-ol (1.5 g, 36%).
9-isobutyl-1-oxa-9-azaspiro[5.5]undecan-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62.9%
With sulfuric acid; at 0 - 20℃;Green chemistry;
General procedure: To a 0C vigorously stirred neat mixture of the respective azacycloalkanone (4.42 mmol) and 3-butenol (4.86 mmol) in a 2 mL glass vial was slowly added 70% H2SO4 (1.5 mL). The stirring was continued overnight, at which point the mixture was diluted by water (5 mL) and the pH adjusted to 9-10 using a saturated aqueous NaOH solution. The mixture was extracted with ethyl acetate (2 x 10 mL), the combined extracts were washed with brine, dried over anhydrous Na2SO4,filtered, and concentrated. Chromatographic purification of the residue on silica gel using 0?5% MeOH in chloroform as eluent afforded analytically pure products 6-20 in the indicated yields.
ethyl 9-hydroxy-6-oxa-2-azaspiro[4.5]decane-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54.6%
With sulfuric acid; at 0 - 20℃;Green chemistry;
General procedure: To a 0C vigorously stirred neat mixture of the respective azacycloalkanone (4.42 mmol) and 3-butenol (4.86 mmol) in a 2 mL glass vial was slowly added 70% H2SO4 (1.5 mL). The stirring was continued overnight, at which point the mixture was diluted by water (5 mL) and the pH adjusted to 9-10 using a saturated aqueous NaOH solution. The mixture was extracted with ethyl acetate (2 x 10 mL), the combined extracts were washed with brine, dried over anhydrous Na2SO4,filtered, and concentrated. Chromatographic purification of the residue on silica gel using 0?5% MeOH in chloroform as eluent afforded analytically pure products 6-20 in the indicated yields.
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; Schlenk technique;
To a solution of <strong>[65-86-1]orotic acid</strong> (2.34 g, 15.0 mmol, 1.00 equiv.) in 20 mL of DMF were added 3-buten-1-ol (1.29 mL, 1.08 g, 15.0 mmol, 1.00 equiv.) and DMAP (91.6 mg, 750 mumol, 0.05 equiv.). After EDC (2.88 g, 15.0 mmol, 1.00 equiv.) was added, the mixture was stirred for 16 h at room temperature. The suspension was quenched by addition of 20 mL of water. The layers were separated and the aqueous layer was extracted with dichloromethane (4 * 20 mL). The organic layers were combined, washed with sat. NaCl solution (15 mL) and dried over Na2SO4. The drying agent was removed by filtration and the volatile components were evaporated in vacuo. The crude product was purified by column chromatography (ethyl acetate/n-pentane = 9/1) to give the product (1.16 g, 5.52 mmol, 37%) as colorless crystals. TLC (ethyl acetate/n-pentane = 9/1): Rf = 0.50 [UV, KMnO4]; mp 197 C; IR (ATR): ? (cm-1) = 3112 (w) (upsilon N-H), 3010 (w) (upsilon C-H), 1736 (m) (upsilon C=O), 1700 (s) (upsilon C=O), 1670 (s) (upsilon C=C), 1633 (s) (upsilon C=O), 1498 (s) (delta N-H), 1421 (s); 1H-NMR (DMSO-d6, 300 K, 500 MHz): delta (ppm) = 2.45 (virt.qt, 3 J ? 3J = 6.6 Hz, 4J ? 1.4 Hz, 2H, H-2'), 4.30 (t, 3J = 6.6 Hz, 2H, H-1'), 5.08 (virt. dq, 3 J = 10.2 Hz, 2J ? 4J = 1.2 Hz, 1H, Htrans-4'), 5.15 (virt. dq, 3 J = 17.1 Hz, 2J ? 4J = 1.7 Hz, 1H, Hcis-4'), 5.84 (ddt, 3J = 17.1, 10.2, 6.6 Hz, 1H, H-3'), 6.02 (s, 1H, H-5), 11.18 (s, 1H, N-H), 11.41 (s, 1H, N-H); 13C NMR (DMSO-d6, 300 K, 126 MHz): delta (ppm) = 32.2 (t, C-2'), 65.4 (t, C-1'), 103.6 (d, C-5), 117.6 (t, C-4'), 134.3 (d, C-3'), 141.5 (s, C-4), 150.9 (s, C-2), 160.2 (s, C-7), 163.8 (s, C-6); MS (EI): m/z(%) = 210 (7) [M]+, 139 (14) [M-C4H7O]+, 73 (100) [C3H5O2]+, 54 (51) [C4H6]+, 44 (82) [C2H4O]+; HRMS (ESI): [M + H]+ calcd.: 211.0713, found: 211.0713.
With dmap; diisopropyl-carbodiimide; In dichloromethane; at 20 - 30℃; for 12h;
2 - ((3-fluoro-4- (methylcarbamoyl) phenyl) amino) -2-methyl-propionic acid (500g, 2.0mol, 1eq), 3- buten-1-ol (140g, 2.0mol, 1.0eq), dimethylaminopyridine (24g, 0.2mol), 1,3- diisopropyl carbodiimide (500g, 4.0mol) and dichloromethane (2L) were sequentially added 10L reaction flask within the control temperature 20 ~ 30 , the reaction was stirred for 12 hours. 2L water was added to the reaction flask, extracted, the aqueous phase was extracted with dichloromethane 2L × 3, dichloromethane layers were combined, washed twice with saturated sodium chloride solution, 2L, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure, 4L of acetone was added with stirring, filtered, and added to the solution with stirring 10L hexane crystallization 2h, give crude intermediate 1 (480g, 1.6mol).
Compound 1 (200 g, 0.91 mol)And 3-buten-1-ol is dissolved in dichloromethane (2000 mL),Then, methanesulfonic acid (526 g, 5.48 mol) was added dropwise to the reaction system at room temperature.After reacting for 12 hours at room temperature, TLC (dichloromethane/methanol volume ratio = 20/1) showed that the reaction was completed.The reaction solution was poured into water, then extracted with methylene chloride, and the organic phase was separated.The organic phase is washed several times with saturated sodium bicarbonate and saturated brine.Then, it is dried and concentrated to give the crude compound 2, which is purified by silica gel column chromatography.Yield: 35.7%.
With pyridine; In dichloromethane; at 0 - 20℃; for 24h;Inert atmosphere;
General procedure: To a 250 mL flame dried Schlenk flask, 1.0 equiv (2.95 g, 10 mmol)of 4,4?-oxybis (benzoyl chloride) dissolved in 80 mL of dry CH2Cl2 was added with stirring under nitrogen atmosphere. The solution was cooled to 0 C and then 2.1 equiv of the 10-undecen-1-ol (3.58 g, 21 mmol) and 2.1 equiv of pyridine (1.66 g, 21 mmol) were slowly added to the solution via syringe. The mixture was allowed to warm to room temperature for 24 h and quenched with addition of 1M HCl (100 mL) and deionized water (100 mL). The organic layer was dried over anhydrous Mg2SO4, filtered, concentrated in vacuum, and purified by column chromatography using n-hexane/ethyl acetate (7/1) as an eluent to yield a white solid. (yield=83%).
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