Pyridine → 1,1-Dimethylethyl 4-[4-(4,5-dihydro-5-(2-fluorophenyl)-3-isoxazolyl)-2-thiazolyl]-1-piperidinecarboxylate

HRID 1802324Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[S:16])[NH2:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:18][C:19]([C:21]1[CH2:25][CH:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[O:23][N:22]=1)=O.N1C=CC=CC=1>C(O)C>[F:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH:24]1[O:23][N:22]=[C:21]([C:19]2[N:15]=[C:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)[S:16][CH:18]=2)[CH2:25]1

Participants

Conditions

Temperature: 77 °C

Procedure

To a solution of 1-tert-butoxycarbonylpiperidine-4-carbothioamide (1 g, 4.10 mmol) in ethanol (10 mL) was added 2-chloro-1-[4,5-dihydro-5-(2-fluorophenyl)-3-isoxazolyl]ethanone (i.e. the product of Step A) (0.99 g) followed by pyridine (0.34 mL, 4.10 mmol). The reaction mixture was heated at 77° C. for 3 h, and then stirred at room temperature overnight. Ethanol was removed from the reaction mixture, and the remaining residue was diluted with ethyl acetate (50 mL). The organic layer was separated, washed with water, saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated under reduced pressure. The resulting oil was purified by column chromatography on silica gel to provide the title compound as a pale yellow sticky oil (1.11 g).

Workup

customEthanol was removed from the reaction mixture
additionthe remaining residue was diluted with ethyl acetate (50 mL)
customThe organic layer was separated
washwashed with water, saturated aqueous sodium chloride solution
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customThe resulting oil was purified by column chromatography on silica gel

Sources & evidence

ORD record: ord-33fa61845470427fb193f2c7c0f39590
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349870B2

Reaction notes

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