Potassium Carbonate → Ethyl 3-(4-((3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)-2,3-difluorophenyl)propanoate

HRID 2177137Notes

Reaction equation

HRID 2177137 reaction equation
CS([O:5][CH2:6][C:7]1[C:8]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[N:9][S:10][C:11]=1[C:12]([F:15])([F:14])[F:13])(=O)=O.[F:23][C:24]1[C:29]([F:30])=[C:28](O)[CH:27]=[CH:26][C:25]=1[CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:8]2[C:7]([CH2:6][O:5][C:28]3[CH:27]=[CH:26][C:25]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:24]([F:23])[C:29]=3[F:30])=[C:11]([C:12]([F:15])([F:14])[F:13])[S:10][N:9]=2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 90404786Ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoateHCID 90418265HCID 90418265, compound

Product 1

HCID 90418385Ethyl 3-(4-((3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)-2,3-difluorophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

Into a 50-mL round-bottom flask, was placed [3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methyl methanesulfonate (101 mg, 0.27 mmol, 1.00 equiv), ethyl 3-(2,3-difluoro-4-hydroxyphenyl)propanoate (prepared according to PCT Application WO2010/048207A2) (81 mg, 0.35 mmol, 1.30 equiv), N,N-dimethyl formamide (3.0 mL), potassium carbonate (113 mg, 0.82 mmol, 3.01 equiv). The resulting solution was stirred overnight at 30° C. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by TLC-Plate with Petroleum ether/EtOAc=6:1. This resulted in 0.10 g (73%) of ethyl 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-2,3-difluorophenyl)propanoate as a light yellow solid. Mass spectrum (ESI, m/z): Calcd. for C22H17ClF5NO3S, 506.1 (M+H). found 506.1.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. customThe reaction was then quenched by the addition of 10 mL of water
  3. extractionThe resulting solution was extracted with 3×10 mL of ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by TLC-Plate with Petroleum ether/EtOAc=6:1
  7. customThis resulted in 0.10 g (73%) of ethyl 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-2,3-difluorophenyl)propanoate as a light yellow solid

Sources & evidence

ORD record
ord-05a274f73ae84538b535f01dbbf48b5a
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

Loading…