4-Fluoroaniline → HCID 71008326, compound

Participants

Reaction Steps

2-Bromo-3-methylbutanoic acid (2.5 g, 14 mmol) was added to 20 mL of SOCl2. The mixture was refluxed for 1 h. The superfluous SOCl2 was removed. The residue was added into the solution of 4-fluorobenzenamine (1.33 g, 12 mmol) in 10 mL of DCM. The mixture was stirred at ambient temperature for 0.5 h and evaporated to dryness. The crude product (3.0 g, 78%) was used in the subsequent step without further purification. A mixture of 5-[4-(2,2,2-Trifluoro-ethoxy)-phenyl]-octahydro-pyrrolo[3,4-c]pyridin-4-one (90 mg, 26 mmol), the crude α-bromoamide (211 mg, 0.77 mmol) and K2CO3 (106 mg, 0.77 mmol) in 15 mL of DMF was heated to 85° C. overnight. The mixture was diluted with water (15 mL) and extracted with EtOAc (2×20 mL), the combined organic layers was washed with water (2×10 mL), brine (2×10 mL), dried with anhydrous Na2SO4 and evaporated to dryness. The residue was purified with prep-TLC (eluting with DCM/MeOH=30:1) to obtain the title compound (33 mg, 25%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.29-7.13 (m, 2H), 7.01-6.84 (m, 4H), 6.69-6.65 (m, 2H), 6.61 (bs, 1H), 4.43-4.35 (m, 2H), 4.03-3.65 (m, 7H), 3.29-3.27 (m, 1H), 2.80 (bs, 1H), 2.10-1.65 (m, 3H), 1.11-1.07 (t, 6H, J=5.4 Hz). LC-MS: 508.2 [M+1]+.

Provenance & Evidence