1,3-Bis(diphenylphosphino)propane → Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-bromo4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene (549.4 mg, 1.468 mmol) in DMSO (6 mL) and MeOH (5 mL) was added Et3 N (448 ul, 3.229 mmol), Pd(OAc)2 (36.2 mg, 0.161 mmol), and 1,3-bis(diphenylphosphino)propane (66.4 mg, 0.161 mmol). To the mixture was induced CO gas for 10 min. The resulting mixture was stirred at 70° C. for 2 days under a current of CO. After the mixture was concentrated, the residue was diluted with EtOAc. The solution was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the residue was chromatographed on silica-gel eluting with n-hexane:EtOAc (5:1, v/v) as eluent to afford 323.0 mg (62%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate as a pale yellow oil. 1H-NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 1.87 (br s, 1H), 1.95–2.10 (m, 3H), 3.34–3.44 (br m, 2H), 3.89 (s, 3H), 3.94 and 4.11–4.26 (br m each, 3H), 7.03–7.11 (m, 1H), 7.75–7.80 (m, 2H); MS (FAB) m/z 354 M++1).

Provenance & Evidence