Tributylphosphine → {(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

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Reaction Steps

A solution of di-tert-butyl azodicarboxylate (18.0 g) in tetrahydrofuran (80 mL) is added dropwise over 45 min to a solution of [(S)-6-hydroxy-2,3-dihydro-benzofuran-3-yl]-acetic acid methyl ester (for preparation see WO 2008001931; 11.0 g), (S)-4-bromo-7-fluoro-indan-1-ol (11.95 g), and tri-n-butyl-phosphine (19.3 mL) in tetrahydrofuran (320 mL) at −10° C. The resulting solution is stirred for 30 min and then partitioned between saturated aqueous NaHCO3 solution and dichloromethane. The aqueous phase is separated and extracted with dichloromethane. The combined organic phases are dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→70:30) to give the title compound. LC (method 1): tR=1.41 min; Mass spectrum (ESI+): m/z=421/423 (Br) [M+H]+.

Provenance & Evidence