2-Chloro-4-phenyl-5-thiazolecarboxylic acid ethyl ester → 2-Chloro-4-phenylthiazole-5-carboxylic acid

HRID 1785487Notes

Reaction equation

HRID 1785487 reaction equation
C([O:3][C:4]([C:6]1[S:10][C:9]([Cl:11])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:5])C>O1CCCC1.[OH-].[Na+]>[Cl:11][C:9]1[S:10][C:6]([C:4]([OH:5])=[O:3])=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:8]=1

Participants

4

Reactant 1

HCID 130418162-Chloro-4-phenyl-5-thiazolecarboxylic acid ethyl ester

Product 1

HCID 130418282-Chloro-4-phenylthiazole-5-carboxylic acidYield 92.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 2-Chloro-4-phenyl-thiazole-5-carboxylic acid ethyl ester (1 g, 3.74 mmol) in tetrahydrofuran (10 ml) and NaOH (15%, 4.8 ml) was stirred at room temperature for 2 hr. After removal of tetrahydrofuran, the aqueous was neutralized with aqueous hydrochloric acid (3 N) to ˜pH=3. The solid was filtered and washed with water, dried in air to give 2-chloro-4-phenyl-thiazole-5-carboxylic acid (0.83 g). The acid was then dissolved in acetonitrile, and EDC (0.62 g, 4 mmol) was added. The mixture was stirred under an ammonia balloon for 2 hrs. Acetonitrile was removed, the residue was diluted with ethyl acetate and washed with water. Ethyl acetate solution was dried over MgSO4. After removal of MgSO4 and solvent, the residue was diluted with tetrahydrofuran (10 ml), followed by adding triethyl amine (0.5 ml). The mixture was cooled in ice, and trifluoroacetic anhydride (0.85 ml) was added dropwise. After the addition, the reaction mixture was stirred overnight at RT. The mixture was then diluted with ethyl acetate and washed with sat. sodium bicarbonate, dried over MgSO4. After removal of the magnesium sulfate and solvent, the residue was purified on Isco (0-20% gradient ethyl acetate in hexane) to give product (287.9 mg, yield 35% overall). 1H-NMR (CDCl3) 8.07-8.13 (m, 2H); 7.47-7.53 (m, 3H); 4.11 (q, 1H); 1.22 (t, 3H). MS M/z 221 (M+1)

Workup

  1. customAfter removal of tetrahydrofuran
  2. filtrationThe solid was filtered
  3. washwashed with water
  4. customdried in air

Sources & evidence

ORD record
ord-d612e4db810f4c038452da2bbc6fc150
Source dataset
uspto-grants-2009_03
Patent number
US07504513B2

Reaction notes

Loading…