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

HRID 852590Notes

Reaction equation

HRID 852590 reaction equation
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]

Participants

4

Reactant 3

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

Product 1

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

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-07e59919ed414231a74392685effb30a
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Reaction notes

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