Triphenylphosphine → (1S,2S)-2-[4-((R)-4-Bromo-7-fluoro-indan-1-yloxy)-phenyl]-cyclopropanecarboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

(1S,2S)-2-(4-Hydroxy-phenyl)-cyclopropanecarboxylic acid ethyl ester (Intermediate 1, 6.51 g, 31.6 mmol), (S)-4-bromo-7-fluoro-indan-1-ol (Intermediate 2, 7.29 g, 31.6 mmol) and triphenyl phosphine (9.11 g, 34.7 mmol) are dissolved in dry tetrahydrofuran (50 mL) and cooled to −20° C. under nitrogen atmosphere. Di-tert-butyl azodicarboxylate (8.00 g, 34.7 mmol) is added and the mixture stirred for 30 minutes at −20° C., then allowed to warm to room temperature and stirred overnight. The solvent is removed under vacuum and the residue purified by flash chromatography (0-10% ethyl acetate in cyclohexane) to give the title compound (Yield 8.23 g). LC (METHOD 2): tR=8.72 min; Mass spectrum (ES+): m/z=460 [M+H+MeCN]+, e.e. 96% by chiral HPLC (Column: Daicel Chiralpak AS-H, 4.6×250 mm, 5 μm Mobile phase: hexane:ethanol 80:20, 1 mL/min, 25° C.) tR=4.96 (4.63) min.

Provenance & Evidence