hexane-2,5-diol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml reaction vessel was charged with 5 g of 2-(2,4-difluorophenyl)-1,2,3-propanetriol, 100 ml of diisopropanol, 2.45 ml of acetic anhydride and 5 g of Novozym 435 made by NOVO NORDISK, Ltd. (derived from Candida antarctica, Enzyme No. 24). The resulting mixture was stirred at 30° C. for 15 hours. After 10 ml of water was added thereto, the reaction liquid was filtered to remove the enzyme. An organic layer of the filtrate was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give 1 g of (S)-2-(2,4-difluorophenyl)-1-acetoxy-1,2-propanediol. The optical purity thereof was 8% ee. A 300 ml reaction vessel the reaction liquid was filtered to remove the enzyme An organic layer of the filtrate was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml reaction vessel was charged with 5 g of 2-(2,4-difluorophenyl)-1,2,3-propanetriol, 100 ml of diisopropanol, 2.45 ml of acetic anhydride and 5 g of Novozym 435 made by NOVO NORDISK, Ltd (derived from Candida antarctica, Enzyme No. 24). The resulting mixture was stirred at 30° C. for 15 hours. After 10 ml of water was added thereto, the reaction liquid was filtered to remove the enzyme. An organic layer of the filtrate was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give 1 g of (S)-2-(2,4-difluorophenyl)-1-acetoxy-1,2-propanediol. The optical purity thereof was 8% ee. A 300 ml reaction vessel the reaction liquid was filtered to remove the enzyme An organic layer of the filtrate was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml reaction vessel was charged with 5 g of 2-(2,4-difluorophenyl)-1,2,3-propanetriol, 100 ml of diisopropanol, 2.45 ml of acetic anhydride and 5 g of Novozym 435 made by NOVO NORDISK, Ltd (derived from Candida antarctica, Enzyme No. 24). The resulting mixture was stirred at 30° C. for 15 hours. After 10 ml of water was added thereto, the reaction liquid was filtered to remove the enzyme. An organic layer of the filtrate was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give 1 g of (S)-2-(2,4-difluorophenyl)-1-acetoxy-1,2-propanediol. The optical purity thereof was 8% ee. A 300 ml reaction vessel the reaction liquid was filtered to remove the enzyme An organic layer of the filtrate was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml reaction vessel was charged with 5 g of 2-(2,4-difluorophenyl)-1,2,3-propanetriol, 100 ml of diisopropanol, 2.45 ml of acetic anhydride and 5 g of Novozym 435 made by NOVO NORDISK, Ltd. (derived from Candida antarctica, Enzyme No. 24). The resulting mixture was stirred at 30° C. for 15 hours. After 10 ml of water was added thereto, the reaction liquid was filtered to remove the enzyme. An organic layer of the filtrate was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give 1 g of (S)-2-(2,4-difluorophenyl)-1-acetoxy-1,2-propanediol. The optical purity thereof was 8% ee. A 300 ml reaction vessel the reaction liquid was filtered to remove the enzyme An organic layer of the filtrate was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1)

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

Procedure: To 2.4 g (0.02 mol) 2,5-hexanediol was added 30 ml tetrahydrofuran, then added 4.8 ml (0.06 mol) pyridine with stirring. To the resulting homogenous mixture was slowly added 5.8 ml (0.05 mol) benzoyl chloride, and the reaction was stirred at room temperature for 1 hour, then heated refluxing for 5 hours. Upon completing the reaction, 20 ml water was added to dissolve the resulting salt. The mixture was extracted with ethyl acetate. The organic phase was separated, washed with saturated saline for two times, and dried over anhydrous sodium sulfate. The solvent was removed. Distillation under reduced pressure gave colorless liquid 2,5-hexanediol dibenzoate, and the yield was 94%. 1HNMR: δ (ppm) 1.36(d, 6H, CH3), 1.86(m, 4H, CH2), 5.21(m, 2H, CH), 7.40-8.16(m, 10H, ArH) the reaction was stirred at room temperature for 1 hour heated refluxing for 5 hours was added to dissolve the resulting salt The mixture was extracted with ethyl acetate The organic phase was separated washed with saturated saline for two times dried over anhydrous sodium sulfate The solvent was removed Distillation under reduced pressure

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

Procedure: To 2.4 g (0.02 mol) 2,5-hexanediol was added 30 ml tetrahydrofuran, then added 4.8 ml (0.06 mol) pyridine with stirring. To the resulting homogenous mixture was slowly added 5.8 ml (0.05 mol) benzoyl chloride, and the reaction was stirred at room temperature for 1 hour, then heated refluxing for 5 hours. Upon completing the reaction, 20 ml water was added to dissolve the resulting salt. The mixture was extracted with ethyl acetate. The organic phase was separated, washed with saturated saline for two times, and dried over anhydrous sodium sulfate. The solvent was removed. Distillation under reduced pressure gave colorless liquid 2,5-hexanediol dibenzoate, and the yield was 94%. 1HNMR: δ (ppm) 1.36(d, 6H, CH3), 1.86(m, 4H, CH2), 5.21(m, 2H, CH), 7.40-8.16(m, 10H, ArH) the reaction was stirred at room temperature for 1 hour heated refluxing for 5 hours was added to dissolve the resulting salt The mixture was extracted with ethyl acetate The organic phase was separated washed with saturated saline for two times dried over anhydrous sodium sulfate The solvent was removed Distillation under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 12.0 g (0.25 mol) of 50% sodium hydride dispersion in mineral oil are freed from the mineral oil with hexane and covered with a layer of 150 cc of absolute 1,2-dimethoxy ethane. A solution of 35.4 g (0.3 mol) of 2,5-hexandiol in 60 cc of absolute 1,2-dimethoxy ethane is added at 5°-10° over a period of 90 minutes and while stirring to the resulting suspension. After stirring for 2 hours at 50°, the mixture is cooled to 10° and 24.2 g (0.2 mol) of allyl-bromide in 40 cc of dry 1,2-dimethoxy ethane are added dropwise. The mixture is slowly heated to 60° and stirred at this temperature for 16 hours. After this period the reaction mixture is cooled to room temperature. After adding 200 cc amounts of ether and water the mixture is vigorously stirred for 15 minutes and the organic phase is separated off in a separating funnel. The ether extract is washed with saturated salt solution, dried over sodium sulphate and evaporated. The residue is purified by chromatography on silica gel with hexane/ethyl acetate (2:1), whereby, according to gas-chromatography, pure 5-allyloxy-2-hexanol is obtained as a colourless oil. After stirring for 2 hours at 50° the mixture is cooled to 10° The mixture is slowly heated to 60° stirred at this temperature for 16 hours is vigorously stirred for 15 minutes the organic phase is separated off in a separating funnel The ether extract is washed with saturated salt solution dried over sodium sulphate evaporated The residue is purified by chromatography on silica gel with hexane/ethyl acetate (2:1), whereby

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

Procedure: 12.0 g (0.25 mol) of 50% sodium hydride dispersion in mineral oil are freed from the mineral oil with hexane and covered with a layer of 150 cc of absolute 1,2-dimethoxy ethane. A solution of 35.4 g (0.3 mol) of 2,5-hexandiol in 60 cc of absolute 1,2-dimethoxy ethane is added at 5°-10° over a period of 90 minutes and while stirring to the resulting suspension. After stirring for 2 hours at 50°, the mixture is cooled to 10° and 24.2 g (0.2 mol) of allyl-bromide in 40 cc of dry 1,2-dimethoxy ethane are added dropwise. The mixture is slowly heated to 60° and stirred at this temperature for 16 hours. After this period the reaction mixture is cooled to room temperature. After adding 200 cc amounts of ether and water the mixture is vigorously stirred for 15 minutes and the organic phase is separated off in a separating funnel. The ether extract is washed with saturated salt solution, dried over sodium sulphate and evaporated. The residue is purified by chromatography on silica gel with hexane/ethyl acetate (2:1), whereby, according to gas-chromatography, pure 5-allyloxy-2-hexanol is obtained as a colourless oil. After stirring for 2 hours at 50° the mixture is cooled to 10° The mixture is slowly heated to 60° stirred at this temperature for 16 hours is vigorously stirred for 15 minutes the organic phase is separated off in a separating funnel The ether extract is washed with saturated salt solution dried over sodium sulphate evaporated The residue is purified by chromatography on silica gel with hexane/ethyl acetate (2:1), whereby

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 300 ml reaction vessel was charged with 5 g of 2-(2,4-difluorophenyl)-1,2,3-propanetriol, 100 ml of diisopropanol, 2.45 ml of acetic anhydride and 5 g of Novozym 435 made by NOVO NORDISK, Ltd. (derived from Candida antarctica, Enzyme No. 24). The resulting mixture was stirred at 30° C. for 15 hours. After 10 ml of water was added thereto, the reaction liquid was filtered to remove the enzyme. An organic layer of the filtrate was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give 1 g of (S)-2-(2,4-difluorophenyl)-1-acetoxy-1,2-propanediol. The optical purity thereof was 8% ee. A 300 ml reaction vessel the reaction liquid was filtered to remove the enzyme An organic layer of the filtrate was dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1)

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

Procedure: To a solution of 2,5-hexanediol (28 mg, 0.240 mmol) in tetrahydrofuran was added an excess of potassium butoxide. The admixture was stirred, briefly, and 2-chloro-4-fluoro-benzonitrile (37 mg, 0.240 mmol) was added. The admixture was stirred at room temperature for 72 hours. Purification by reverse phase high pressure chromatography eluting with a solvent gradient (15% of 0.1% formic acid/CH3CN in 0.1% formic acid/water to 100% of 0.1% formic acid/water) provided 28.4 mg of 2-chloro-4-(4-hydroxy-1-methyl-pentyloxy)-benzonitrile. 1H NMR (CDCl3) δ 7.50 (d, 1H), 6.95 (m, 1H), 6.79 (br d, 1H), 4.43 (m, 1H), 3.79 (m, 1H), 1.89-1.40 (m, 4H), 1.30 (d, 3H), 1.17 (d, 3H); MS m/z 253. The admixture was stirred at room temperature for 72 hours Purification by reverse phase high pressure chromatography eluting with a solvent gradient (15% of 0.1% formic acid/CH3CN in 0.1% formic acid/water to 100% of 0.1% formic acid/water)