Ethyl bromopyruvate → Ethyl 2-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)-1,3-thiazole-4-carboxylate

HRID 17490

Reaction equation

HRID 17490 reaction equation
Br[CH2:2][C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:10]([C:12]1[C:17]2[N:18]=[C:19]([C:21](=[S:23])[NH2:22])[O:20][C:16]=2[C:15]([F:24])=[C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:13]=1[CH3:31])#[N:11].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>O.C1(C)C=CC=CC=1>[C:10]([C:12]1[C:17]2[N:18]=[C:19]([C:21]3[S:23][CH:2]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[N:22]=3)[O:20][C:16]=2[C:15]([F:24])=[C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:13]=1[CH3:31])#[N:11]

Participants

7

Reactant 4

HCID 66144Ethyl bromopyruvateHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 860973994-Cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carbothioamide

Product 1

HCID 68584336Ethyl 2-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)-1,3-thiazole-4-carboxylateYield 91.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
125 °C

Procedure

Ethyl 3-bromopyruvate (72.2 μl, 0.518 mmol) was added to a toluene (10 ml) solution of 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carbothioamide (I-196-1) (124 mg, 0.398 mmol), followed by heating under reflux in an oil bath at 125° C. for 2 hours. After cooling to room temperature, p-toluenesulfonic acid monohydrate (15.2 mg, 0.080 mmol) was added to the reaction liquid, followed by heating under reflux in an oil bath at 125° C. for 15 hours. After cooling to room temperature, an aqueous saturated sodium hydrogencarbonate solution (50 ml) and water (50 ml) were added, followed by extraction with ethyl acetate (50 ml×2). The organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution (50 ml) and saturated brine (50 ml), and dried over anhydrous sodium sulfate. After concentration, the resulting residue was purified by silica gel column chromatography (eluent, chloroform:ethyl acetate=100:1→25:1) to obtain the entitled compound (148 mg, 91.2%) as a pale yellow solid.

Workup

  1. temperatureby heating
  2. temperatureAfter cooling to room temperature
  3. temperatureby heating
  4. temperatureunder reflux in an oil bath at 125° C. for 15 hours
  5. temperatureAfter cooling to room temperature
  6. extractionfollowed by extraction with ethyl acetate (50 ml×2)
  7. washThe organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution (50 ml) and saturated brine (50 ml)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationAfter concentration
  10. customthe resulting residue was purified by silica gel column chromatography (eluent, chloroform:ethyl acetate=100:1→25:1)

Sources & evidence

ORD record
ord-1171c5d92c7945a39487ce52620c7f22
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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