2-Bromothiazole → 1,1-Dimethylethyl 4-hydroxy-4-(2-thiazolyl)-1-piperidinecarboxylate

HRID 1408349Notes

Reaction equation

[Li]CCCC.Br[C:7]1[S:8][CH:9]=[CH:10][N:11]=1.[C:12]([N:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>CCOCC.C1COCC1>[C:15]([O:14][C:12]([N:19]1[CH2:24][CH2:23][C:22]([OH:25])([C:7]2[S:8][CH:9]=[CH:10][N:11]=2)[CH2:21][CH2:20]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled (−78° C.) and stirred solution of n-BuLi (2.6 mL, 1.05 eq., 10.0 M in hexanes) in dry Et2O (20 mL) was added dropwise a solution of 2-bromothiazole (4.0 g, 24.4 mmol) in THF (10 mL) over a 10 minute period. After the yellow mixture had been stirred at −78° C. for 30 minutes, a solution of 1-Boc-4-piperidone (4.9 g, 1 eq.) in THF (20 mL) was added slowly. The mixture was then continued to stir for another 30 minutes before the reaction was quenched by addition of water (5 mL). The mixture was warmed to room temperature and extracted with EtOAc. The organic phase was separated, washed with brine and dried over Na2SO4. After removal of the solvent, the crude product was purified on silica gel (45% EtOAc in hexanes) to afford the desired product as a thick oil.

Workup

stirringto stir for another 30 minutes before the reaction
customwas quenched by addition of water (5 mL)
temperatureThe mixture was warmed to room temperature
extractionextracted with EtOAc
customThe organic phase was separated
washwashed with brine
dry with materialdried over Na2SO4
customAfter removal of the solvent
customthe crude product was purified on silica gel (45% EtOAc in hexanes)

Sources & evidence

ORD record: ord-0191e3fa78264b4abaeaa71428feba68
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921350B2

Reaction notes

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