Sodium Hydroxide → 3-(3-Chloro-4-pyrrolidin-1-ylmethyl-phenyl)-3-hydroxy-cyclobutanecarboxylic acid cyclopropylmethyl-amide

Participants

Reaction Steps

To a solution of crude intermediate 17, 3-(3-chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid (˜4.3 mL ˜0.65 mmol) was added aminomethylcyclopropane (0.112 ml, 1.29 mmol) and T3P (50% solution in EtOAc, 0.62 ml, 0.97 mmol). The resulting reaction mixture was stirred at RT for 1 hr and then 25 ml of 1N NaOH and 100 ml of EtOAc were added and the layers were separated. The aqueous layer was subjected to EtOAc extraction (2×60 ml) again and the combined organic layers were dried over MgSO4 and evaporated. The residue was purified by flash column chromatography using a 40 g ISCO™ column, eluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH. The product containing fractions were collected and concentrated under reduced pressure to give the title compound (101 mg, 43% yield). Rf=0.80 (20% MeOH/CH2Cl2+0.2% NH4OH); LRMS m/z Calcd for C20H27ClN2O2, 362.9, found, 363.2 (M+1) APCI; 400 MHz 1H NMR (CDCl3) δ 7.44-7.38 (m, 2H), 7.28 (dd, J=7.9, 2.6 Hz, 1H), 6.40 (br apt t, J=5.4 Hz, 1H), 3.69 (s, 2H), 3.10-3.04 (m, 2H), 2.76-2.68 (m, 3H), 2.57-2.42 (m, 6H), 1.78-1.69 (m, 4H), 0.94-0.84 (m, 1H), 0.48-0.40 (m, 2H), 0.18-0.12 (m, 2H); 100 MHz 13C NMR (CDCl3) δ 176.7, 146.1, 135.3, 133.9, 130.8, 126.3, 123.6, 74.0, 56.7, 54.3, 44.9, 41.1, 40.7, 33.1, 23.7, 10.8, 3.7.

Provenance & Evidence