Methyl 4-chloroacetoacetate → Methyl (2'-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-2,5'-bi-1,3-thiazol-4-yl)acetate

HRID 561203Notes

Reaction equation

[F:1][C:2]([F:25])([F:24])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17](=[S:19])[NH2:18])=[CH:15][N:16]=2)[CH2:8][CH2:7]1.Cl[CH2:27][C:28](=O)[CH2:29][C:30]([O:32][CH3:33])=[O:31]>CO.O>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17]3[S:19][CH:27]=[C:28]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[N:18]=3)=[CH:15][N:16]=2)[CH2:8][CH2:7]1

Participants

Conditions

Temperature: 82.5 °C

Procedure

A mixture of 2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carbothioamide (240 mg, 0.62 mmol) and methyl 4-chloroacetoacetate (73 μL, 0.62 mmol) in methanol (3 mL) was heated in a sealed tube at 80-85° C. overnight. After cooling, the mixture was diluted with water and extracted with EtOAc. The EtOAc extract was washed twice with water, dried (Na2SO4) and concentrated. The crude material was purified by column chromatography on silica gel (eluting with 30-60% EtOAc/hexanes) to give the title compound as a pale yellow gum.

Workup

temperatureAfter cooling
extractionextracted with EtOAc
extractionThe EtOAc extract
washwas washed twice with water
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe crude material was purified by column chromatography on silica gel (eluting with 30-60% EtOAc/hexanes)

Sources & evidence

ORD record: ord-84dadda0bd434f54a7d7e256accde99e
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063224B2

Reaction notes

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