(S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester → (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxy-propionic acid

Participants

Reaction Steps

A solution of the compound of Formula II(a)(ii), (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxypropionic acid benzyl ester (1.27 g, 2.63 mmol) in THF was stirred with 10% Pd/C (400 mg) under a hydrogen atmosphere for 1 hour. The reaction mixture was filtered and concentrated to give the compound of Formula II(a)(i), (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxy-propionic acid (1.03 g, ˜100%) as a sticky, off-white foam. NMR (d6-DMSO, 400 MHz) δ (ppm) 8.34 (d, J=8 Hz, 1H), 7.12 (d, J=8 Hz, 1H), 6.66 (t, J=76 Hz, 1H), 6.62 (t, J=76 Hz, 1H), 4.57-4.51 (m, 1H), 4.37-4.29 (m, 1H), 4.15-4.09 (m, 1H), 4.04-3.97 (m, 2H), 3.92-3.83 (m, 1H), 1.37 (s, 9H). Scheme VII outlines the synthesis of compound intermediates of Formula IV(b) and Formula V(b) which are used in the preparation of the compounds of Formula (I) wherein R2 and/or R3 is a —CH2—O—CH3 moiety.

Provenance & Evidence