Thiazole → Tert-butyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]piperidine-1-carboxylate

HRID 410515Notes

Reaction equation

C([Li])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([C:24](=[O:26])[CH3:25])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>C1COCC1>[OH:26][C:24]([CH:21]1[CH2:20][CH2:19][N:18]([C:16]([O:15][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:17])[CH2:23][CH2:22]1)([C:7]1[S:6][CH:10]=[CH:9][N:8]=1)[CH3:25]

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyl lithium (0.281 mL, 0.702 mmol) was added dropwise to a stirred, cooled (−78° C.) mixture of thiazole (0.050 mL, 0.702 mmol) in THF (2.55 mL) and the mixture was stirred at −78° C. for 30 min. A solution of 4-acetyl-piperidine-1-carboxylic acid tert-butyl ester in THF (0.638 mL) was then added dropwise. Temperature was maintained at −78° C. for 30 min and then allowed to reach room temperature. The reaction was quenched with saturated NH4Cl solution and extracted with EtOAc (×2). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography to give tert-butyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]piperidine-1-carboxylate (180 mg, 0.576 mmol, 90%) as a colorless oil.

Workup

temperaturecooled
temperatureTemperature was maintained at −78° C. for 30 min
customto reach room temperature
customThe reaction was quenched with saturated NH4Cl solution
extractionextracted with EtOAc (×2)
washThe combined organics were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-fc93da516e3943d5b181f6b32a65ec2c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759366B2

Reaction notes

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