Biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form

An efficient four-step biotransformation-mediated synthesis of (1S)-1-(2,6-dichloro-3-fluorophenyl)ethanol in enantiomerically pure form is described. This compound is a key intermediate required for the preparation of PF-2341066, a potent inhibitor of c-Met/ALK that is currently in clinical development. The described synthesis was used to manufacture 6 kg of the title compound and can also be employed to produce the corresponding (1R)-enantiomer.

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(1S)-1-(2,6-Dichloro-3-fluorophenyl)ethanolC8H7Cl2FOEe = 98%αD20=+6.9±1.1 (c 0.87, MeOH)Source of chirality: pig liver esterase