Cyclopropylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2-cyclopropylamino-3,6-difluorobenzoic acid ethyl ester

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Reaction Steps

A solution of 4-[(S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester (Example 2b, 5.4 g, 13.9 mmol), cyclopropylamine (40 mL, 577 mmol), and dimethyl sulfoxide (28 mL) in a sealed glass tube is heated at 100° C. for 27 hours. The excess amine is removed by blowing in compressed air before the solution is concentrated under high vacuum. The residue is then purified by column chromatography (1:1:8 ethyl acetate/chloroform/hexanes) to afford the title compound (4.80 g). 1H NMR (CDCl3): δ 7.42 (bs, 1H), 5.69 (ddd, 1H), 4.76–4.61 (m, 1H), 4.37–4.19 (m, 3H), 3.81–3.66 (m, 1H), 3.65–3.43 (m, 2H), 3.39–3.28 (m, 1H), 2.98–2.82 (m, 1H), 2.30–2.09 (m, 1H), 1.98–1.82 (m, 1H), 1.45 (s, 9H), 1.34 (t, 3H), 0.72–0.68 (m, 2H), 0.67–0.44 (m, 2H).

Provenance & Evidence