Dichloromethane → Chloromethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate

HRID 571347Notes

Reaction equation

HRID 571347 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].[Cl:28][CH2:29]Cl.CCCCCC>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:18])([CH3:17])[C:14]([O:16][CH2:29][Cl:28])=[O:15])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8058HexaneHCID 64929Fenofibric AcidHCID 516892Sodium Bicarbonate

Product 1

HCID 57586167Chloromethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoateYield 101%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent

Procedure

A mixture of 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid (10.0 g, 31.4 mmol), sodium bicarbonate (13.2 g, 47.1 mmol, 1.5 eq) and tetrabutylammonium hydrogensulfate (2.1 g, 6.3 mmol, 0.2 eq) in water (150 mL) was stirred at room temperature for 15 min. Dichloromethane (150 mL) was added and the mixture was cooled in ice. Chloromethyl sulfochloridate (4.2 mL, 47.1 mmol, 1.5 eq) was added and the mixture was stirred overnight at room temperature. The layers were separated, the organic phase was washed with water (50 mL) and brine, then dried over sodium sulfate. The drying agent was filtered off and the solution was concentrated by rotary evaporation to leave a thick oil. Hexane (50 mL) and seeds were added and rotary evaporation was continued at room temperature to leave chloromethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate 1 as a white solid (11.6 g, 101% yield). 1H-NMR (CDCl3) δ 7.73 (d, 2 H), 7.70 (d, 2 H), 7.44 (d, 2 H), 6.87 (d, 2 H), 5.77, (s, 2 H), 1.70 (s, 6 H) ppm.

Workup

  1. temperaturethe mixture was cooled in ice
  2. additionChloromethyl sulfochloridate (4.2 mL, 47.1 mmol, 1.5 eq) was added
  3. stirringthe mixture was stirred overnight at room temperature
  4. customThe layers were separated
  5. washthe organic phase was washed with water (50 mL) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationThe drying agent was filtered off
  8. concentrationthe solution was concentrated by rotary evaporation
  9. customto leave a thick oil
  10. customrotary evaporation
  11. customwas continued at room temperature

Sources & evidence

ORD record
ord-37e1aed844594d4e9253087802b89949
Source dataset
uspto-grants-2015_05
Patent number
US09024069B2

Reaction notes

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