Sodium Bromide → 1-[3-(5-Bromo-2-methoxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone

HRID 237300노트

반응식

HRID 237300 반응식
[F:1][C:2]([F:19])([F:18])[C:3]([N:5]1[CH2:8][CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH2:6]1)=[O:4].[Na+].[Br-:21].OOS([O-])=O.[K+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>CC(C)=O.O.CCOC(C)=O>[Br:21][C:14]1[CH:13]=[CH:12][C:11]([O:16][CH3:17])=[C:10]([CH:15]=1)[CH2:9][CH:7]1[CH2:6][N:5]([C:3](=[O:4])[C:2]([F:1])([F:18])[F:19])[CH2:8]1

참가 물질

8

반응물 4

HCID 253881Sodium BromideHCID 656671Sodium PyrosulfiteHCID 23707502Potassium hydroxy sulfiteHCID 584050552,2,2-Trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanone

생성물 1

HCID 584051591-[3-(5-Bromo-2-methoxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone수율 53.5%

시약·촉매·용매 3

HCID 180Acetone용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2,2,2-trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanone (95 mg, 0.35 mmol) in acetone (2 mL) and water (2 mL) was added NaBr (143 mg, 1.40 mmol) followed by Oxone (210 mg, 0.35 mmol). After 5 h, 10% sodium metabisulfite solution was added. After 1 h, EtOAc was added and the aqueous portion extracted twice with EtOAc. The combined organics were dried (Na2SO4) and concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (66 mg, 53%). MS (ESI): mass calcd. for C13H13BrF3NO2, 352.1; m/z found, 354.1 [M+H]+. 1H NMR (CDCl3): 7.32 (dd, J=8.7, 2.5 Hz, 1H), 7.17 (d, J=2.5 Hz, 1H), 6.75 (t, J=10.2 Hz, 1H), 4.43 (dd, J=9.6, 8.4 Hz, 1H), 4.26-4.14 (m, 1H), 4.09 (dd, J=9.6, 5.7 Hz, 1H), 3.89 (dd, J=10.7, 5.7 Hz, 1H), 3.81 (s, 3H), 3.14-2.96 (m, 1H), 2.90 (d, J=7.8 Hz, 2H).

후처리

  1. waitAfter 1 h
  2. extractionthe aqueous portion extracted twice with EtOAc
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by RP HPLC (basic conditions)

출처 및 근거

ORD 기록
ord-9564c82bd14a4847bbd25b435b2711fa
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642583B2

반응 노트

불러오는 중…