Hydrogen Bromide → Methyl 5-bromo-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate

HRID 852590ノート

反応式

HRID 852590 の反応式
N[C:2]1[CH:3]=[C:4]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[BrH:19].N([O-])=O.[Na+]>>[Br:19][C:2]1[CH:3]=[C:4]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

参加物

4

反応物 3

HCID 260Hydrogen Bromide2 回HCID 23668193Sodium NitriteHCID 69357536Methyl 5-amino-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate

生成物 1

HCID 69356077Methyl 5-bromo-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate収率 18%

反応条件

温度
0 °C

実験手順

To a solution of methyl 5-amino-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate (D150) (650 mg, 2.6 mmol, 1 equiv) in a 48% aqueous HBr solution at 0° C. was added NaNO2 portionwise and the resulting mixture was stirred at 0° C. for 30 min. CuBr (260 mg, 1.82 mmol, 0.7 equiv) in a 48% aqueous HBr solution (1 ml) was added and the resulting mixture stirred at 90° C. for 1 h then cooled to room temperature and partitioned between H2O and AcOEt. The two layers were separated and the organic phase was dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 2/1) gave methyl 5-bromo-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate (D156) (145 mg, 18%) as a white solid. [M+H]+=318.1, RT=2.51 min.

後処理

  1. stirringthe resulting mixture stirred at 90° C. for 1 h
  2. temperaturethen cooled to room temperature
  3. custompartitioned between H2O and AcOEt
  4. customThe two layers were separated
  5. dry with materialthe organic phase was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel (iso-hexane/AcOEt: 2/1)

出典と根拠

ORDレコード
ord-07e59919ed414231a74392685effb30a
出典データセット
uspto-grants-2007_08
特許番号
US07253198B2

反応ノート

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