(2R)-pentan-2-ol → 2-{[(1R)-1-Methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

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Reaction Conditions

Reaction Steps

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).

Provenance & Evidence