(2R)-pentan-2-ol

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium t-butoxide (27.3 g, 284 mmol) was added portionwise to (R)-2-pentanol (140 ml) at room temperature, the mixture was stirred until homogeneous. 2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (18.0 g, 71.0 mmol) was added and the reaction mixture heated at 50° C. for 160 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (500 ml) and water (500 ml). The organic phase was washed with saturated sodium chloride solution (100 ml), dried (MgSO4), filtered and evaporated. The residue was triturated with ether and the solid material filtered. The precipitate was re-washed with ether and the filtrates combined and evaporated. The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) and purified on a reverse phase (C18) column (330 g) using a gradient of 25-65% acetonitrile (+0.1% TFA)-water (+0.1% TFA) over 8 column volumes, the fractions were immediately neutralised with saturated aqueous sodium carbonate solution. Appropriate fractions were combined and partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The organic phase was dried (MgSO4), filtered and evaporated to give the title compound as a pale cream foam (5.05 g). The reaction was cooled to room temperature partitioned between ethyl acetate (500 ml) and water (500 ml) The organic phase was washed with saturated sodium chloride solution (100 ml) dried (MgSO4) filtered evaporated The residue was triturated with ether the solid material filtered The precipitate was re-washed with ether evaporated The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) purified on a reverse phase (C18) column (330 g) partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate The organic phase was dried (MgSO4) filtered evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium t-butoxide (27.3 g, 284 mmol) was added portionwise to (R)-2-pentanol (140 ml) at room temperature, the mixture was stirred until homogeneous. 2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (18.0 g, 71.0 mmol) was added and the reaction mixture heated at 50° C. for 160 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (500 ml) and water (500 ml). The organic phase was washed with saturated sodium chloride solution (100 ml), dried (MgSO4), filtered and evaporated. The residue was triturated with ether and the solid material filtered. The precipitate was re-washed with ether and the filtrates combined and evaporated. The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) and purified on a reverse phase (C18) column (330 g) using a gradient of 25-65% acetonitrile (+0.1% TFA)-water (+0.1% TFA) over 8 column volumes, the fractions were immediately neutralised with saturated aqueous sodium carbonate solution. Appropriate fractions were combined and partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The organic phase was dried (MgSO4), filtered and evaporated to give the title compound as a pale cream foam (5.05 g). The reaction was cooled to room temperature partitioned between ethyl acetate (500 ml) and water (500 ml) The organic phase was washed with saturated sodium chloride solution (100 ml) dried (MgSO4) filtered evaporated The residue was triturated with ether the solid material filtered The precipitate was re-washed with ether evaporated The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) purified on a reverse phase (C18) column (330 g) partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate The organic phase was dried (MgSO4) filtered evaporated

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

Procedure: To a mixture of 1-chloroethyl chloroformate (1.19 mL), pyridine (1.49 mL), and THF (100 mL), (R)-(−)-2-pentanol [CSA No. 31087-44-2] (1 mL) dissolved in THF (3 mL) was added at −78° C. After stirring the mixture overnight at room temperature, ethyl acetate and heptane were added to the reaction mixture. The resulting mixture was sequentially washed with 0.5 N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, water, and saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure to obtain the captioned compound (1.8 g) as a crude product. was added at −78° C The resulting mixture was sequentially washed with 0.5 N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, water, and saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate The resulting mixture was filtered the filtrate obtained was concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium t-butoxide (27.3 g, 284 mmol) was added portionwise to (R)-2-pentanol (140 ml) at room temperature, the mixture was stirred until homogeneous. 2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (18.0 g, 71.0 mmol) was added and the reaction mixture heated at 50° C. for 160 hours. The reaction was cooled to room temperature and partitioned between ethyl acetate (500 ml) and water (500 ml). The organic phase was washed with saturated sodium chloride solution (100 ml), dried (MgSO4), filtered and evaporated. The residue was triturated with ether and the solid material filtered. The precipitate was re-washed with ether and the filtrates combined and evaporated. The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) and purified on a reverse phase (C18) column (330 g) using a gradient of 25-65% acetonitrile (+0.1% TFA)-water (+0.1% TFA) over 8 column volumes, the fractions were immediately neutralised with saturated aqueous sodium carbonate solution. Appropriate fractions were combined and partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The organic phase was dried (MgSO4), filtered and evaporated to give the title compound as a pale cream foam (5.05 g). The reaction was cooled to room temperature partitioned between ethyl acetate (500 ml) and water (500 ml) The organic phase was washed with saturated sodium chloride solution (100 ml) dried (MgSO4) filtered evaporated The residue was triturated with ether the solid material filtered The precipitate was re-washed with ether evaporated The crude material (ca. 10 g) was dissolved in DMSO:methanol (1:1) purified on a reverse phase (C18) column (330 g) partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate The organic phase was dried (MgSO4) filtered evaporated