1,2-Dichloroethane → (R)-N'-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-fluorobenzohydrazide

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoic acid (4.0 g, 14.2 mmol) in THF (100 mL) were added 4-fluorobenzoic hydrazide (2.40 g, 15.6 mmol), HOBt (1.91 g, 14.1 mmol), EDC (4.07 g, 21.2 mmol) and Et3N (3.0 mL, 21.5 mmol) at −20° C. sequentially. After addition, the mixture was stirred at −20° C. for 30 min., then room temperature overnight. The reaction was quenched by adding ice-water. After removal of the THF, the residue was extracted with EtOAc (300 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. The filtrate was concentrated and purified by flash chromatography to give the title compound (R)—N′-(2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-3-methylbutanoyl)-4-fluorobenzohydrazide (4.28 g, 72%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 9.61 (b, 2H), 8.00 (dd, J=5.5, 9.0 Hz, 2H), 7.51 (d, J=8.6 Hz, 1H), 7.25 (t, J=9.0 Hz, 2H), 6.71 (d, J=8.6 Hz, 1H), 5.53 (d, J=7.4 Hz, 1H), 4.06 (d, J=7.4 Hz, 1H), 2.35 (s, 3H), 1.45 (s, 3H), 1.40 (s, 3H).

Provenance & Evidence