Pyridine → N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)acetamide

HRID 1715226Notes

Reaction equation

[C:1]([C:4]1[S:8][C:7]([NH2:9])=[N:6][C:5]=1[CH3:10])(=[O:3])[CH3:2].N1C=CC=CC=1.[C:17](Cl)(=[O:19])[CH3:18]>C1COCC1.C(Cl)Cl>[C:1]([C:4]1[S:8][C:7]([NH:9][C:17](=[O:19])[CH3:18])=[N:6][C:5]=1[CH3:10])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

5-Acetyl-2-amino-4-methylthiazole (P5)(Flrochem)(12.4 g, 79 mmol) is suspended in THF/DCM 3:2 mixture (150 ml). The mixture is cooled down to 0° C. and pyridine (16 ml) is added, followed by the dropwise addition of acetyl chloride (8.43 ml, 119 mmol, 1.5 eq.). The mixture is stirred 2 hours at 0° C. As the acetylation is complete, the reaction is quenched with addition of water (70 ml) and diluted with EtOAc (100 ml). The two phases are separated and the organic phase is washed with one portion of 10% citric acid solution. Organic layer is dried over MgSO4, filtrated and evaporated. The resulting crude mass is purified by crystallization in EtOAc/Cyclohexane mixture, to obtain N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)acetamide (P6) as a colorless powder (13.1 g, 83.6% yield). 1H NMR (DMSO-d6) δ: 2.17 (s, 3H), 2.47 (s, 3H), 2.56 (s, 3H), 12.44 (br s, 1H). M− (ESI): 197.3; M+ (ESI): 199.3. HPLC (method A), Rt: 1.7 min (purity: 99.7%).

Workup

customthe reaction is quenched with addition of water (70 ml)
additiondiluted with EtOAc (100 ml)
customThe two phases are separated
washthe organic phase is washed with one portion of 10% citric acid solution
dry with materialOrganic layer is dried over MgSO4
filtrationfiltrated
customevaporated
customThe resulting crude mass is purified by crystallization in EtOAc/Cyclohexane mixture

Sources & evidence

ORD record: ord-92845478cba64cf58275b52b05a14244
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07799814B2

Reaction notes

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