Pyrrolidine → 6-Fluoro-2,2-bis(fluoromethyl)chroman-4-one

HRID 1913293Notes

Reaction equation

HRID 1913293 reaction equation
[F:1][CH2:2][C:3]([CH2:5][F:6])=[O:4].[F:7][C:8]1[CH:9]=[CH:10][C:11](O)=[C:12]([C:14](=[O:16])[CH3:15])[CH:13]=1.N1CCCC1>CO>[F:7][C:8]1[CH:13]=[C:12]2[C:11](=[CH:10][CH:9]=1)[O:4][C:3]([CH2:5][F:6])([CH2:2][F:1])[CH2:15][C:14]2=[O:16]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 959922-Acetyl-4-fluorophenolHCID 2283971,3-Difluoroacetone

Product 1

HCID 498578376-Fluoro-2,2-bis(fluoromethyl)chroman-4-oneYield 67.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1,3-difluoroacetone (4.90 g, 52.1 mmol), MeOH (100 mL), and 1-(5-fluoro-2-hydroxyphenyl)ethanone (6.69 g, 43.4 mmol, Aldrich Chemical) was stirred at ambient temperature and pyrrolidine (4.31 mL, 52.1 mmol) was added. The reaction was heated at 60° C. for 21 hours, then concentrated and purified by silica gel chromatography (gradient elution, 0-25% EtOAc/hexanes) to provide the title compound (6.70 g, 29.1 mmol, 67%) as a brown oil. MS (DCI) m/z 248 (M+NH4)+.

Workup

  1. concentrationconcentrated
  2. custompurified by silica gel chromatography (gradient elution, 0-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d5c2877bc1f7421b8d6dd0cf7bbce9a9
Source dataset
uspto-grants-2013_12
Patent number
US08609692B2

Reaction notes

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