Ethyl 4-chloroacetoacetate → 2-(3-Hydroxy-2-pyridinyl)-4-thiazoleacetic Acid Ethyl Ester

HRID 260029Notes

Reaction equation

HRID 260029 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[N:7]=[C:8]([C:11]2C=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[S:9][CH:10]=1)[CH3:2].OC1C(C(=S)N)=[N:22]C=CC=1.ClCC(=O)CC(OCC)=O.[Li+].[Br-]>C1COCC1>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[N:7]=[C:8]([C:11]2[C:12]([OH:17])=[CH:13][CH:14]=[CH:15][N:22]=2)[S:9][CH:10]=1)[CH3:2]

Participants

6

Reactant 4

HCID 69484Ethyl 4-chloroacetoacetateHCID 82050Lithium BromideHCID 1360263402-(2-Hydroxyphenyl)-4-thiazoleacetic Acid Ethyl EsterHCID 1360468883-Hydroxythiopicolinamide

Product 1

HCID 1359793022-(3-Hydroxy-2-pyridinyl)-4-thiazoleacetic Acid Ethyl EsterYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The procedure used for the preparation of 4a was repeated with 3-hydroxy-2-pyridinecarbothioamide 3c (358 mg, 2.32 mmol), ethyl 4-chloroacetoacetate (0.628 mL, 4.65 mmol), and LiBr (202 mg, 2.32 mmol) in dry THF (6 mL) to give 4c (552 mg, 90%) as a white solid after chromatographic purification on silica gel (gradient EtOAc/CH2Cl2 : 0-12%) and recrystallization from CH2Cl2 /hexane. mp 85.5°-86.5° C.; IR (KBr) 3400, 1723, 1436, 1202, 1178 cm-1 ; 1H NMR (DMSO-d6) δ1.16 (3H, t, J=7.1 Hz, CH3), 3.93 (2H, s, CH2), 4.08 (2H, q, J=7.1 Hz, CH2), 7.37 (1H, dd, J=8.3 and 4.2 Hz, Ar), 7.45 (1H, d, J=8.3 Hz, Ar), 7.66 (1H, s), 8.15 (1H, d, J=4.2 Hz, Ar), 11.64 (1H, s, OH); FDMS m/z 264 (M+); Anal. Calcd for C12H12N2O3S: C, 54.53; H, 4.58; N, 10.60. Found: C, 54.83; H, 4.66; N, 10.30.

Sources & evidence

ORD record
ord-6eaa1b1f9b29498a8f87c6fffec19a27
Source dataset
uspto-grants-1996_06
Patent number
US05525599

Reaction notes

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