Pyrrolidine → 7-Chloro-2-(difluoromethyl)-2-methylchroman-4-one

HRID 1913311Notes

Reaction equation

HRID 1913311 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[C:4]([OH:11])[CH:3]=1.[F:12][CH:13]([F:17])[C:14]([CH3:16])=O.N1CCCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:8](=[O:10])[CH2:9][C:14]([CH:13]([F:17])[F:12])([CH3:16])[O:11]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 10515131-(4-Chloro-2-hydroxyphenyl)ethanoneHCID 34947711,1-Difluoropropan-2-one

Product 1

HCID 673620997-Chloro-2-(difluoromethyl)-2-methylchroman-4-oneYield 84%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-(4-Chloro-2-hydroxyphenyl)ethanone (8.07 g, 47.3 mmol), MeOH (81 mL), 1,1-difluoroacetone (4.89 g, 52.0 mmol), and pyrrolidine (4.30 ml, 52.0 mmol) were stirred at ambient temperature for 45 hours, at 35° C. for 7 hours, then at 50° C. for 3 hours. The reaction mixture was concentrated, diluted with MTBE (75 mL), then washed with water (40 mL), 2N HCl (2×25 mL), brine (20 mL), 2N NaOH (2×20 mL), and brine (2×20 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give the title compound (9.78 g, 39.7 mmol, 84% yield) as a brown oil. MS (DCI/NH3) m/z 264 (M+NH4)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with MTBE (75 mL)
  3. washwashed with water (40 mL), 2N HCl (2×25 mL), brine (20 mL), 2N NaOH (2×20 mL), and brine (2×20 mL)
  4. dry with materialThe organic portion was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a6d06ce577ba423ab2201f35a3466bbc
Source dataset
uspto-grants-2013_12
Patent number
US08609692B2

Reaction notes

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