(2R)-propane-1,2-diol

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

Procedure: To a suspension of (2R)-1,2-propanediol (1.9 mL) in toluene (20 mL) was added triethylamine (8.3 mL) and 4-dimethylaminopyridine (32 mg). The mixture was ice-cooled and 1,1′,1″-(chloromethylidyne)tris-benzene (6.6 g) was added and the mixture stirred at ambient temperature for 20 h. The reaction mixture was diluted with toluene then extracted with ammonium chloride solution (×2), then brine (×1) and the organic layer was dried (MgSO4), filtered and evaporated. The resulting oil was triturated with iso-hexane to give subtitle compound as a white solid. Yield: 4 g cooled then extracted with ammonium chloride solution (×2) brine (×1) and the organic layer was dried (MgSO4) filtered evaporated The resulting oil was triturated with iso-hexane

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: Triisopropylsilyl chloride (83.8 mL, 390 mmol) was added slowly over 15 minutes to a solution of (2R)-propane-1,2-diol (29.7 g, 390 mmol) in DMF at 0° C. (100 mL) keeping the internal temperature below 15° C. This was followed by addition of imidazole (66.4 g, 975 mmol) and the reaction mixture was allowed to warm to RT and stirred under argon for 20 hours. The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL). The organic layer was separated and washed with 1M hydrochloric acid followed by saturated brine solution. The organic layer was dried (MgSO4), filtered and evaporated. Purification by distillation at 10 mmHg, 90-104° C., afforded the title compound as colourless oil (69.5 g). 1H NMR δ (CDCl3): 1.05 (s, 18H), 1.05-1.1 (m, 3H), 1.05 (d, 3H), 2.55 (s, 1H), 3.45 (dd, 1H), 3.7 (dd, 1H), 3.85 (m, 1H). the internal temperature below 15° C The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL) The organic layer was separated washed with 1M hydrochloric acid The organic layer was dried (MgSO4) filtered evaporated Purification by distillation at 10 mmHg, 90-104° C.

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

Procedure: Dimethylaminopyridine (165 mg, 1.35 mmol) was added to a solution of (R)-propane-1,2-diol (10.3 g, 135.4 mmol) and trityl chloride (38.1 g 136.7 mmol) in DCM (400 mL) at 0° C. Triethylamine (47.2 mL, 338.4 mmol) was then added dropwise to this mixture. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was washed with 1.0 N aq HCl (200 mL), washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to give (R)-1-(trityloxy)propan-2-ol (36.4 g, 84%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.43-7.39 (m, 6H) 7.34-7.31 (m, 6H) 7.26-7.22 (m, 3H), 4.70 (d, 1H), 3.82-3.76 (m, 1H), 2.95-2.92 (dd, 1H), 2.70-2.67 (dd, 1H), 1.06 (d, 3H). The reaction mixture was washed with 1.0 N aq HCl (200 mL) washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography

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

Procedure: Dimethylaminopyridine (165 mg, 1.35 mmol) was added to a solution of (R)-propane-1,2-diol (10.3 g, 135.4 mmol) and trityl chloride (38.1 g 136.7 mmol) in DCM (400 mL) at 0° C. Triethylamine (47.2 mL, 338.4 mmol) was then added dropwise to this mixture. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was washed with 1.0 N aq HCl (200 mL), washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to give (R)-1-(trityloxy)propan-2-ol (36.4 g, 84%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.43-7.39 (m, 6H) 7.34-7.31 (m, 6H) 7.26-7.22 (m, 3H), 4.70 (d, 1H), 3.82-3.76 (m, 1H), 2.95-2.92 (dd, 1H), 2.70-2.67 (dd, 1H), 1.06 (d, 3H). The reaction mixture was washed with 1.0 N aq HCl (200 mL) washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography

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

Procedure: Dimethylaminopyridine (82 mg, 0.67 mmol) was added to a solution of (R)-propane-1,2-diol (5.17 g, 67.9 mmol) and trityl chloride (19.2 g 68.9 mmol) in DCM (200 mL) at 0° C. Triethylamine (23.5 mL, 168.6 mmol) was then added dropwise to this mixture. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was washed with 1.0 N aq HCl (50 mL), washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to give (R)-1-(trityloxy)propan-2-ol (18.6 g, 86%) as a white solid. 1H NMR (DMSO-d6): δ 7.43-7.22 (m, 15H), 4.64 (d, 1H), 3.78 (m, 1H), 2.94 (dd, 1H), 2.70 (dd, 1H), 1.06 (d, 3H). The reaction mixture was washed with 1.0 N aq HCl (50 mL) washed with brine (50 mL) dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by silica gel chromatography

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

Procedure: Triisopropylsilyl chloride (83.8 mL, 390 mmol) was added slowly over 15 minutes to a solution of (2R)-propane-1,2-diol (29.7 g, 390 mmol) in DMF at 0° C. (100 mL) keeping the internal temperature below 15° C. This was followed by addition of imidazole (66.4 g, 975 mmol) and the reaction mixture was allowed to warm to RT and stirred under argon for 20 hours. The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL). The organic layer was separated and washed with 1M hydrochloric acid followed by saturated brine solution. The organic layer was dried (MgSO4), filtered and evaporated. Purification by distillation at 10 mmHg, 90-104° C., afforded the title compound as colourless oil (69.5 g). 1H NMR δ (CDCl3): 1.05 (s, 18H), 1.05-1.1 (m, 3H), 1.05 (d, 3H), 2.55 (s, 1H), 3.45 (dd, 1H), 3.7 (dd, 1H), 3.85 (m, 1H). the internal temperature below 15° C The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL) The organic layer was separated washed with 1M hydrochloric acid The organic layer was dried (MgSO4) filtered evaporated Purification by distillation at 10 mmHg, 90-104° C.

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: A solution of tert-butyldimethylchlorosilane (9.9 g, 65.7 mmol) in dichloromethane was added dropwise to a solution of (R)-(−)-1,2-propanediol (5 g, 65.7 mmol) and imidazole (4.47 g, 65.7 mmol) in anhydrous dichloromethane at 0° C. The reaction mixture was stirred at 0° C. for 30 min before dilution with dichloromethane. The solution was washed with water three times followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure to afford 12.0 g (96%) of (2R)-1-(tert-Butyldimethylsiloxy)propan-2-ol. The solution was washed with water three times followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure

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

Procedure: A solution of tert-butyldimethylchlorosilane (9.9 g, 65.7 mmol) in dichloromethane was added dropwise to a solution of (R)-(−)-1,2-propanediol (5 g, 65.7 mmol) and imidazole (4.47 g, 65.7 mmol) in anhydrous dichloromethane at 0° C. The reaction mixture was stirred at 0° C. for 30 min before dilution with dichloromethane. The solution was washed with water three times followed by the addition of brine. The organic layer was separated, dried through a MgSO4 pad and concentrated under reduced pressure to afford 12.0 g (96%) of (2R)-1-(tert-Butyldimethylsiloxy)propan-2-ol. The solution was washed with water three times followed by the addition of brine The organic layer was separated dried through a MgSO4 pad concentrated under reduced pressure

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

Procedure: Triisopropylsilyl chloride (83.8 mL, 390 mmol) was added slowly over 15 minutes to a solution of (2R)-propane-1,2-diol (29.7 g, 390 mmol) in DMF at 0° C. (100 mL) keeping the internal temperature below 15° C. This was followed by addition of imidazole (66.4 g, 975 mmol) and the reaction mixture was allowed to warm to RT and stirred under argon for 20 hours. The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL). The organic layer was separated and washed with 1M hydrochloric acid followed by saturated brine solution. The organic layer was dried (MgSO4), filtered and evaporated. Purification by distillation at 10 mmHg, 90-104° C., afforded the title compound as colourless oil (69.5 g). the internal temperature below 15° C The reaction was quenched with 1M hydrochloric acid/diethyl ether (300 mL/800 mL) The organic layer was separated washed with 1M hydrochloric acid The organic layer was dried (MgSO4) filtered evaporated Purification by distillation at 10 mmHg, 90-104° C.