Acetic Acid → 2-(4-Bromo-3-fluorophenyl)pyrrolidine

HRID 415152Notes

Reaction equation

HRID 415152 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][CH2:11][N:12]=2)=[CH:4][C:3]=1[F:13].[BH3-]C#N.[Na+].C(O)(=O)C>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][CH2:11][NH:12]2)=[CH:4][C:3]=1[F:13]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 666213385-(4-bromo-3-fluorophenyl)-3,4-dihydro-2H-pyrrole

Product 1

HCID 534036242-(4-Bromo-3-fluorophenyl)pyrrolidineYield 98%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-(4-bromo-3-fluorophenyl)-3,4-dihydro-2H-pyrrole ((12.7 g, 52.7 mmol) in 360 mL methanol was added NaBH3CN (6.6 g, 105 mmol) at 0° C. The resulting solution was adjusted to pH=6 with acetic acid. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with 2 N HCl and the methanol was removed by evaporation. The residue was diluted with water, the aqueous phase adjusted to pH=10 with NaOH, extracted with ethyl acetate, dried by Na2SO4, concentrated and the residue was purified by chromatography on silica gel to give 2-(4-bromo-3-fluorophenyl)pyrrolidine as a yellow solid (12.5 g, yield 98%). LC-MS (ESI) m/z: 244 (M+1)+.

Workup

  1. customThe reaction was quenched with 2 N HCl
  2. customthe methanol was removed by evaporation
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate
  5. dry with materialdried by Na2SO4
  6. concentrationconcentrated
  7. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-90e9127cecf34070a4e5dca854305378
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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