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

온도

70 °C

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).

1. customfor 10 min
2. concentrationAfter the mixture was concentrated
3. additionthe residue was diluted with EtOAc
4. washThe solution was washed with brine
5. dry with materialdried over Na2SO4
6. customThe solvent was removed under a reduced pressure
7. customthe residue was chromatographed on silica-gel
8. washeluting with n-hexane:EtOAc (5:1

ORD 기록

ord-4102c1ab981c47a28d0893bc320fa521

출처 데이터셋

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07179819B2