6-(Trifluoromethyl)nicotinic acid → 4-Methoxymethyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazole-5-carboxylic acid methyl ester

HRID 2233288Notes

Reaction equation

HRID 2233288 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[S:8])=[CH:5][N:4]=1.FC(F)(F)C1C=CC(C(O)=O)=CN=1.ClCC1OC(C2(C)CCCCC2)=NC=1C.ClCC1SC(C2CCC(F)(F)CC2)=NC=1COC.[CH3:60][O:61][C:62](=[O:70])[CH:63](Cl)[C:64](=O)[CH2:65][O:66][CH3:67]>C(O)C>[CH3:60][O:61][C:62]([C:63]1[S:8][C:7]([C:6]2[CH:5]=[N:4][C:3]([C:2]([F:1])([F:12])[F:13])=[CH:11][CH:10]=2)=[N:9][C:64]=1[CH2:65][O:66][CH3:67])=[O:70]

Participants

7

Reactant 5

HCID 27775516-(Trifluoromethyl)nicotinic acidHCID 27778866-(Trifluoromethyl)thionicotinamideHCID 592953925-Chloromethyl-4-methyl-2-(1-methyl-cyclohexyl)-oxazoleHCID 59295416Methyl 2-chloro-4-methoxy-3-oxobutanoateHCID 592954495-Chloromethyl-2-(4,4-difluoro-cyclohexyl)-4-methoxymethyl-thiazole

Product 1

HCID 592953904-Methoxymethyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazole-5-carboxylic acid methyl esterYield 11.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

10.5 g 6-Trifluoromethyl-thionicotinamide (derived from 6-Trifluoromethyl-nicotinic acid according to the method described for 5-Chloromethyl-4-methyl-2-(1-methyl-cyclohexyl)-oxazole and 5-Chloromethyl-2-(4,4-difluoro-cyclohexyl)-4-methoxymethyl-thiazole) and 10.0 g 2-Chloro-4-methoxy-3-oxo-butyric acid methyl ester were dissolved in 100 ml ethanol and heated under reflux overnight. The cooled reaction mixture was evaporated under reduced pressure and the resulting residue was purified by RP-HPLC to obtain 1.9 g 4-Methoxymethyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazole-5-carboxylic acid methyl ester.

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 RP-HPLC

Sources & evidence

ORD record
ord-b4cfbf2419f242eaab6dffa4c6727eef
Source dataset
uspto-grants-2010_05
Patent number
US07709481B2

Reaction notes

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