Methyl 2-chloro-4-methoxy-3-oxobutanoate → 2-(4,4-Difluoro-cyclohexyl)-4-methoxymethyl-thiazole-5-carboxylic acid methyl ester

HRID 2233287Notes

Reaction equation

HRID 2233287 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][CH:5]([C:8](=[S:10])[NH2:9])[CH2:4][CH2:3]1.[CH3:12][O:13][C:14](=[O:22])[CH:15](Cl)[C:16](=O)[CH2:17][O:18][CH3:19]>C(O)C>[CH3:12][O:13][C:14]([C:15]1[S:10][C:8]([CH:5]2[CH2:6][CH2:7][C:2]([F:1])([F:11])[CH2:3][CH2:4]2)=[N:9][C:16]=1[CH2:17][O:18][CH3:19])=[O:22]

Participants

4

Reactant 2

HCID 59295416Methyl 2-chloro-4-methoxy-3-oxobutanoateHCID 592954654,4-Difluorocyclohexane-1-carbothioamide

Product 1

HCID 592955222-(4,4-Difluoro-cyclohexyl)-4-methoxymethyl-thiazole-5-carboxylic acid methyl esterYield 33.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

7.0 g 4,4-Difluoro-cyclohexanecarbothioic acid amide and 8.46 g 2-Chloro-4-methoxy-3-oxo-butyric acid methyl ester were dissolved in 70 ml ethanol and heated under reflux overnight. The cooled reaction mixture was evaporated under reduced pressure and the resulting residue was purified by silica chromatography with the eluent n-heptane:ethyl acetate=4:1=>2:1 to obtain 4.0 g 2-(4,4-Difluoro-cyclohexyl)-4-methoxymethyl-thiazole-5-carboxylic acid methyl ester as an oil.

Workup

  1. temperatureheated
  2. temperatureunder reflux overnight
  3. customThe cooled reaction mixture
  4. customwas evaporated under reduced pressure
  5. customthe resulting residue was purified by silica chromatography with the eluent n-heptane

Sources & evidence

ORD record
ord-fb664793b7484604a68c0114f0f7e0e4
Source dataset
uspto-grants-2010_05
Patent number
US07709481B2

Reaction notes

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