Dichloromethane → HCID 67168162, compound

HRID 1506285Notes

Reaction equation

HRID 1506285 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([OH:14])=[O:13])[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:20]Cl>CO>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([O:14][CH3:20])=[O:13])[C:8]=2[C:15]([F:17])([F:18])[F:16])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6344Dichloromethane2×HCID 58374151HCID 58374151, compound

Product 1

HCID 67168162HCID 67168162, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylic acid (Intermediate I-5D, 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) (1.17 mL, 2.33 mmol) slowly over 10 min. During the addition, the solution remained colorless and the evolution of gas nitrogen was noted. Toward the end of the addition, the bubbling ceased and the solution became pale yellow. The reaction mixture was stirred overnight. 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 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate (0.509 g, 1.88 mmol, 97% yield) as a yellow oil. The product had an HPLC with a ret. time=2.52 min. (condition A); 1H NMR (400 MHz, CDCl3) δ ppm 4.05 (s, 3H), 7.50-7.64 (m, 3H), and 7.70 (d, J=7.48 Hz, 2H).

Workup

  1. additionDuring the addition
  2. additionToward the end of the addition
  3. washwashed with brine (20 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-028cecde7b5a46a4aa2e6062b83c1d20
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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