(3R)-butane-1,3-diol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (R)-1,3-butanediol (2 g), triethylamine (4 mL) and t-butyldiphenylchlorosilane (6.7 g) in CH2Cl2 (80 mL) was stirred at r.t. for 15 h. Saturated NH4Cl was added and the mixture was extracted with ethyl acetate. The combined organics were dried (MgSO4) and concentrated. Flash chromatography of the residue (9:1 hexane/ethyl acetate) provided the title compound as an oil. the mixture was extracted with ethyl acetate The combined organics were dried (MgSO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal (2.01 g), p-toluenesulphonic acid monohydrate (0.316 g) and (R)-(-)-butane-1,3-diol (98%, 1.37 g) in toluene (130 ml) was heated under reflux with a Dean-Stark trap for 20 h. The mixture was concentrated to ca. 30 ml and purified by FCC eluting with System A (1:4) to give the title product (1.78 g,) as a white solid. δ(CDCl3) 1.23 (d, J 6 Hz, 3H, CH3CH--O), 1.42 (d, J 7 Hz, 6H, (CH3)2CH), 1.55-1.8 (m, 2H, OCH(CH3)CH2CH2O), 3.20 (septet, J 7 Hz, 1H, (CH3)2CH), 3.7-3.9 (m, 2H, CH2O), 4.05-4.16 (m, 1H, O--CH(CH3)), 4.95 (d, J 5 Hz, 1H, CH=CHCH(O)2), 5.32 (dd, J 15 and 5 Hz, 1H, NCH=CH), 6.76 (dd, J 15 and 1 Hz, 1H, NCH=CH), 6.89 (t, J 9 Hz, 2H, C-3 and C-5 protons of 4-(4-fluorophenyl)), 7.11 (t, J 9 Hz, 2H, C-3 and C-5 protons of 5-(4-fluorophenyl)), 7.39 and 7.27 (2 dd, J 9 and 6 Hz, 4H, C-2 and C-6 protons of both 4-fluorophenyls). was heated under reflux with a Dean-Stark trap for 20 h The mixture was concentrated to ca. 30 ml purified by FCC eluting with System A (1:4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (3.18 g, 133 mmol) was dispersed in 100 ml DMF and added with 1,3-(R)-butanediol (5.03 g, 55.8 mmol) while being cooled with ice. The mixture after being cooled with ice for another one hour was stirred at room temperature for 2 hours and then added with 4-chlorobenzonitrile (16.8 g, 122 mmol) at room temperature, followed by being reacted for 20 hours. After completion of the reaction, the reaction mixture was carefully added with 5 ml water to inactivate excess sodium hydride, followed by distilling out DMF in vacuum. The resulting mixture after being added with 200 ml of water was subjected to processes of extraction of an organic matter with ethyl acetate, washing with a solution of saturated sodium chloride and distillation of the solvent, followed by distillation of the oily residue thus obtained using Kugelloa distilling equipment at a temperature of 275° C. and a pressure of 0.5 mmHg thereby obtaining the intended product (13.3 g, 45.4 mmol, 81%). while being cooled with ice The mixture after being cooled with ice for another one hour by being reacted for 20 hours After completion of the reaction by distilling out DMF in vacuum The resulting mixture after being added with 200 ml of water was subjected to processes of extraction of an organic matter with ethyl acetate washing with a solution of saturated sodium chloride and distillation of the solvent followed by distillation of the oily residue thus obtained distilling equipment at a temperature of 275° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Put 1.0 g (11.1 mmol) (3R)-butane-1,3-diol in 20 ml THF at 0° C. Add dropwise 5.55 ml (11.1 mmol) of a 2 M solution of the phosphazene base P2-tert.-butyl in THF and stir for 30 min at 0° C. Then add 2.27 g (11.65 mmol) tert.-butyl bromoacetate. Stir for 30 min at 0° C., then leave to return to RT and stir for a further 1 h. Then dilute with ethyl acetate, add water and acidify with 10% citric acid solution. Extract once more with ethyl acetate, combine the organic phases, wash once with satd. sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. Purify by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 8:2). 730 mg (32.2% of theor.) of the target compound is obtained, which according to 1H-NMR (doublet at 1.18 ppm) contains approx. 10% of the regioisomer [(1R)-3-hydroxy-1-methylpropyl]oxy}acetic acid tert.-butyl ester. at 0° C Stir for 30 min at 0° C. leave to return to RT stir for a further 1 h Extract once more with ethyl acetate wash once with satd sodium chloride solution, dry over magnesium sulphate concentrate by evaporation Purify by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 8:2) 730 mg (32.2% of theor.) of the target compound is obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The microorganisms usable in the present invention include those belonging to the genera Rhodococcus, Gordona and Streptomyces and capable of acting on an enantiomorphic mixture of 1,3-butanediol so as to leave (R)-1,3-butanediol as such and those belonging to the genera Rhodococcus and Gordona capable of acting on an enantiomorphic mixture of 1,3-butanediol so as to leave (S)-1,3-butanediol as such.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (R)-1,3-butanediol (2 g), triethylamine (4 mL) and t-butyldiphenylchlorosilane (6.7 g) in CH2Cl2 (80 mL) was stirred at r.t. for 15 h. Saturated NH4Cl was added and the mixture was extracted with ethyl acetate. The combined organics were dried (MgSO4) and concentrated. Flash chromatography of the residue (9:1 hexane/ethyl acetate) provided the title compound as an oil. the mixture was extracted with ethyl acetate The combined organics were dried (MgSO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-Butane-1,3-diol (5.00 mL), tert-butylchlorodimethylsilane (8.82 g), N,N-dimethylpyridin-4-amine (0.34 g) and triethylamine (23.2 mL) were suspended in dichloromethane (60 mL) and stirred at room temperature overnight. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organics were dried over magnesium sulfate and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant: 5-10% ethyl acetate/hexane) to furnish to afford the title compound (8.33 g) having the following physical properties. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and dichloromethane The organics were dried over magnesium sulfate concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant: 5-10% ethyl acetate/hexane) to furnish

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After adding pyridine (100 ml) to (R)-1,3-butanediol (86.0 g), the solution was cooled to −25° C. under nitrogen atmosphere. A solution of p-toluenesulfonyl chloride (200 g) in pyridine (200 ml) was slowly added dropwise thereto at a temperature ranging from −20 to −10° C. The mixture was stirred for 1 hour at a temperature ranging from −20 to −10° C. A small amount of water was added to the reaction mixture to stop the reaction and the solution was extracted with toluene and water. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to obtain (R)-3-hydroxy-1-(p-toluenesulfonyloxy)butane (209 g) as light brown oil. The oil thus obtained was used in the next step as such without purification. ranging from −20 to −10° C ranging from −20 to −10° C the reaction the solution was extracted with toluene and water The organic layer was washed with water dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: After adding pyridine (100 ml) to (R)-1,3-butanediol (86.0 g), the solution was cooled to −25° C. under nitrogen atmosphere. A solution of p-toluenesulfonyl chloride (200 g) in pyridine (200 ml) was slowly added dropwise thereto at a temperature ranging from −20 to −10° C. The mixture was stirred for 1 hour at a temperature ranging from −20 to −10° C. A small amount of water was added to the reaction mixture to stop the reaction and the solution was extracted with toluene and water. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to obtain (R)-3-hydroxy-1-(p-toluenesulfonyloxy)butane (209 g) as light brown oil. The oil thus obtained was used in the next step as such without purification. ranging from −20 to −10° C ranging from −20 to −10° C the reaction the solution was extracted with toluene and water The organic layer was washed with water dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal (2.01 g), p-toluenesulphonic acid monohydrate (0.316 g) and (R)-(-)-butane-1,3-diol (98%, 1.37 g) in toluene (130 ml) was heated under reflux with a Dean-Stark trap for 20 h. The mixture was concentrated to ca. 30 ml and purified by FCC eluting with System A (1:4) to give the title product (1.78 g), as a white solid. δ(CDCl3) 1.23 (d, J 6 Hz, 3H, CH3CH--O), 1.42 (d, J 7 Hz, 6H, (CH3)2CH), 1.55-1.8 (m, 2H, OCH(CH3)CH2CH2O), 3.20 (septet, J 7 Hz, 1H, (CH3)2CH), 3.7-3.9 (m, 2H, CH2O), 4.05-4.16 (m, 1H, O--CH(CH3)), 4.95 (d, J 5 Hz, 1H, CH=CHCH(O)2), 5.32 (dd, J 15 and 5 Hz, 1H, NCH=CH), 6.76 (dd, J 15 and 1 Hz, 1H, NCH=CH), 6.89 (t, J 9 Hz, 2H, C-3 and C-5 protons of 4-(4-fluorophenyl)), 7.11 (t, J 9 Hz, 2H, C-3 and C-5 protons of 5-(4-fluorophenyl)), 7.39 and 7.27 (2 dd, J 9 and 6 Hz, 4H, C-2 and C-6 protons of both 4-fluorophenyls). was heated under reflux with a Dean-Stark trap for 20 h The mixture was concentrated to ca. 30 ml purified by FCC eluting with System A (1:4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The microorganisms usable in the present invention include those belonging to the genera Rhodococcus, Gordona and Streptomyces and capable of acting on an enantiomorphic mixture of 1,3-butanediol so as to leave (R)-1,3-butanediol as such and those belonging to the genera Rhodococcus and Gordona and capable of acting on an enantiomorphic mixture of 1,3-butanediol so as to leave (S)-1,3-butanediol as such.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal (2.01 g), p-toluenesulphonic acid monohydrate (0.316 g) and (R)-(-)-butane-1,3-diol (98%, 1.37 g) in toluene (130 ml) was heated under reflux with a Dean-Stark trap for 20 h. The mixture was concentrated to ca. 30 ml and purified by FCC eluting with System A (1:4) to give the title product (1.78 g,) as a white solid. δ(CDCl3) 1.23 (d, J 6 Hz, 3H, CH3CH--O), 1.42 (d, J 7 Hz, 6H, (CH3)2CH), 1.55-1.8 (m, 2H, OCH(CH3)CH2CH2O), 3.20 (septet, J 7 Hz, 1H, (CH3)2CH), 3.7-3.9 (m, 2H, CH2O), 4.05-4.16 (m, 1H, O--CH(CH3)), 4.95 (d, J 5 Hz, 1H, CH=CHCH(O)2), 5.32 (dd, J 15 and 5 Hz, 1H, NCH=CH), 6.76 (dd, J 15 and 1 Hz, 1H, NCH=CH), 6.89 (t, J 9 Hz, 2H, C-3 and C-5 protons of 4-(4-fluorophenyl)), 7.11 (t, J 9 Hz, 2H, C-3 and C-5 protons of 5-(4-fluorophenyl)), 7.39 and 7.27 (2 dd, J 9 and 6 Hz, 4H, C-2 and C-6 protons of both 4-fluorophenyls). was heated under reflux with a Dean-Stark trap for 20 h The mixture was concentrated to ca. 30 ml purified by FCC eluting with System A (1:4)