Cyclopropylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,5-difluorobenzoic acid ethyl ester

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Reaction Steps

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,5-trifluorobenzoic acid ethyl ester (Example 2a, 1.95 g, 5.01 mmol) and cyclopropylamine (14.0 mL, 201 mmol) in dimethyl sulfoxide (5 mL) is heated in a sealed glass tube for 44.5 hours at 100° C. Compressed air is blown into the black solution to remove excess cyclopropylamine. The solution is concentrated under high vacuum and purified by flash column chromatography (1:9 ethyl acetate/hexanes) to afford the title compound (1.77 g). 1H NMR (CDCl3): δ 7.32 (dd, 1H), 4.81–4.67 (bs, 1H), 4.35–4.16 (m, 3H), 3.95–3.40 (m, 4H), 2.92–2.80 (m, 1H), 2.25–2.08 (m, 1H), 1.97–1.77 (m, 1H), 1.46 (s, 9H), 1.34 (t, 3H), 0.72–0.63 (m, 2H), 0.57–0.49 (m, 2H).

Provenance & Evidence