Methanol → 7-Chloro-2-(fluoromethyl)-2-methylchroman-4-one

HRID 1913309Notes

Reaction equation

HRID 1913309 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.CO.[F:14][CH2:15][C:16](=O)[CH3:17].N1CCCC1>CC(OC)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:8](=[O:10])[CH2:9][C:16]([CH2:15][F:14])([CH3:17])[O:11]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 9889FluoroacetoneHCID 31268PyrrolidineHCID 10515131-(4-Chloro-2-hydroxyphenyl)ethanone

Product 1

HCID 673626587-Chloro-2-(fluoromethyl)-2-methylchroman-4-oneYield 94.3%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

1-(4-Chloro-2-hydroxyphenyl)ethanone (10.2 g, 59.8 mmol), MeOH (100 mL), fluoroacetone (5.00 g, 65.8 mmol), and pyrrolidine (5.44 ml, 65.8 mmol) were stirred at ambient temperature. After 3 days, LCMS showed complete reaction. The reaction mixture was diluted with MTBE (250 mL), washed with water (100 mL), 2N HCl (2×50 mL), brine (50 mL), 2N NaOH (2×50 mL), and brine (2×50 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to provide the title compound (12.9 g, 56.4 mmol, 94% yield) as a brown oil. MS (DCI/NH3) m/z 246 (M+NH4)+.

Workup

  1. customreaction
  2. washwashed with water (100 mL), 2N HCl (2×50 mL), brine (50 mL), 2N NaOH (2×50 mL), and brine (2×50 mL)
  3. dry with materialThe organic portion was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-92f2eb682fda4c6e8e0425b2f1cfe45c
Source dataset
uspto-grants-2013_12
Patent number
US08609692B2

Reaction notes

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