Sodium Carbonate → N-cyclopropyl-3-(4,4-diethoxybutyl)-4-fluorobenzamide

Temperatur

80 °C

A solution of 3-butenal diethyl acetal (144 mg, 1 mmol) and 9-BBN (0.5 M in THF, 2.2 mL, 1.1 mmol) was stirred at RT for 1 h. The mixture was concentrated and to the residue were added benzene (2 mL), EtOH (1 mL), aqueous Na2CO3 solution (2M, 1 mL), 3-bromo-4-fluoro-N-cyclopropylbenzamide (127 mg, 0.5 mmol) and Pd(Ph3P)4 (40 mg). The resulting mixture was stirred at 80° C. for 2 h. The mixture was then cooled to RT and diluted with ethyl acetate (10 mL) and washed with water. The organic layer was separated and concentrated. The residue was purified by column chromatography (SiO2; EtOAc/hexane 1:3) to afford N-cyclopropyl-3-(4,4-diethoxybutyl)-4-fluorobenzamide (151 mg, 93%). This material was dissolved in acetone (1 mL) and 3 N HCl solution (0.2 mL) and stirred at RT for 1 h. The mixture was neutralized with NaHCO3 solution and extracted with ethyl acetate (3×5 mL). The organic layer was dried and concentrated to afford N-cyclopropyl-4-fluoro-3-(4-oxo-butyl)-benzamide (110 mg, 94%). 1H NMR (CDCl3) δ 9.76 (s, 1H), 7.63 (dd, 1H, J=7.5 and 2.2 Hz,), 7.58 (m, 1H), 7.03 (t, 1H, J=9.0 Hz,), 6.47 (s, NH, 1H), 2.87 (m, 1H), 2.69 (t, 2H, J=7.5 Hz,), 2.48 (m, 2H), 1.95 (m, 2H), 0.86 (m, 2H) and 0.62 (m, 2H).

1. concentrationThe mixture was concentrated and to the residue
2. temperatureThe mixture was then cooled to RT
3. washwashed with water
4. customThe organic layer was separated
5. concentrationconcentrated
6. customThe residue was purified by column chromatography (SiO2; EtOAc/hexane 1:3)

ORD-Eintrag

ord-6acb1d04a85546bfb4027103cf1e03b9

Quelldatensatz

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07547711B2