Methanol → 2-(4-Chloro-phenyl)-4-methoxycarbonylmethyl-thiazole-5-carboxylic acid

HRID 554853Notes

Reaction equation

HRID 554853 reaction equation
[C:1]([CH2:4][C:5]1[N:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[S:8][C:9]=1[C:10]([OH:12])=[O:11])([OH:3])=[O:2].S(=O)(=O)(O)O.[CH3:25]O>>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C:7]2[S:8][C:9]([C:10]([OH:12])=[O:11])=[C:5]([CH2:4][C:1]([O:3][CH3:25])=[O:2])[N:6]=2)=[CH:18][CH:17]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 674612304-Carboxymethyl-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid

Product 1

HCID 674601572-(4-Chloro-phenyl)-4-methoxycarbonylmethyl-thiazole-5-carboxylic acid

Procedure

Mix 4-carboxymethyl-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid (145 g, 482 mmol) in MeOH (900 mL) and treat with sulfuric acid (1.20 mL, 21.68 mmol). Stir the mixture at reflux overnight and then begin distilling the MeOH to concentrate the solution. Collect about 300 mL of MeOH and then reflux for an additional 5 h. Filter the reaction mixture and cool the filtrate in an ice bath for one hour. Collect the yellow precipitate by filtration and rinse with cool MeOH. Dry the solid in a vacuum oven at 45° C. overnight to give 105 g of the title compound. Concentrate the above filtrate to about 200 mL volume and collect 20 g of additional material. 1H NMR (DMSO-d6, 500 MHz): δ 13.72 (br s, 1H), 8.00 (d, 2H, J=8.4), 7.59 (d, 2H, J=8.8), 4.21 (s, 2H), 3.64 (s, 3H).

Workup

  1. temperatureat reflux overnight
  2. distillationbegin distilling the MeOH
  3. concentrationto concentrate the solution
  4. customCollect about 300 mL of MeOH
  5. temperaturereflux for an additional 5 h
  6. filtrationFilter the reaction mixture
  7. temperaturecool the filtrate in an ice bath for one hour
  8. customCollect the yellow precipitate
  9. filtrationby filtration
  10. washrinse with cool MeOH
  11. customDry the solid in a vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-66b007cf2d364cbd82c15f8f1c4c8d25
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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