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

HRID 237300ノート

反応式

HRID 237300 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 180Acetone溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-9564c82bd14a4847bbd25b435b2711fa
出典データセット
uspto-grants-2014_02
特許番号
US08642583B2

反応ノート

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