Sodium Bromide → Methyl 2-(bromoacetyl)pent-2-enoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-chloro-2-propylideneacetoacetic acid methyl ester (818 mg: 4.29 mMol.) in dimethylformamide (2.1 ml) is added sodium bromide (957 mg: 9.3 mMol.), and the mixture is stirred at 22° C. for 2 hours to give a solution of 4-bromo-2-propylideneacetoacetic acid methyl ester [NMR δ(CDCl3) ppm: 1.15(t, J=7.5 Hz, 3H), 2.50(q, J=7.5 Hz, 3H), 2.53(q, J=7.5 Hz, 2H), 3.82(s, 3H), 3.90(s, 3H), 4.15(s, 2H), 4.22 (s, 2H), 7.10(t, J=7.5 Hz, 1H), 7.12(t, J=7.5 Hz, 1H)⟧ This solution is diluted with dichloromethane (0.7 ml), mixed with a solution of thiourea (354 mg: 4.65 mMol.) in dimethylformamide (1.4 ml), and stirred at -15° C. to 30° C. for 25 minutes. The reaction mixture is washed with aqueous sodium hydroxide and brine, concentrated at less than 15° C. under reduced pressure, mixed with acetone (1.8 ml), and neutralized with 35% hydrochloric acid. The separating crystals are washed with acetone and dried over to give (Z)-2-(2-aminothiazol-4-yl)-2-pentenoic acid methyl ester hydrochloride (452 mg).

Provenance & Evidence