Dichloromethane → Methyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate

HRID 1506280Notes

Reaction equation

HRID 1506280 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=[O:17])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:20]Cl>CO>[C:1]1([C:7]2[C:11]([C:12]([F:13])([F:14])[F:15])=[C:10]([C:16]([O:18][CH3:20])=[O:17])[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6344Dichloromethane2×HCID 583740941236188-80-9

Product 1

HCID 13508376Methyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylic acid (Intermediate I-3D, 0.500 g, 1.94 mmol) in dichloromethane (5 mL) and methanol (1 mL) at room temperature was added trimethyldiazomethane (2.0 M in ether) (1.26 mL, 2.53 mmol) slowly over 5 min. The resulting reaction mixture was stirred for 30 min. The reaction mixture was diluted with dichloromethane (40 mL) and washed with brine (20 mL). The aqueous layer was extracted with dichloromethane (2×20 mL), and the organic layers were combined and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded methyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate (0.513 g, 1.89 mmol, 97% yield) as a yellow oil. The product had an HPLC ret. time=2.55 min. (condition A); LC/MS M+1=272.0; 1H NMR (400 MHz, CDCl3) δ ppm 4.07 (s, 3H), 7.47-7.56 (m, 3H), and 7.59 (d, J=7.04 Hz, 2H).

Workup

  1. customThe resulting reaction mixture
  2. washwashed with brine (20 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-89a36b5aca514122bf92d40b1d74e215
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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