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

HRID 1038030Notes

Reaction equation

Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[Li]CCCC.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].O>CCOCC>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][C:22]([OH:25])([C:2]2[S:3][CH:4]=[CH:5][N:6]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: -78 °C

Procedure

2-Bromo-thiazole (0.27 mL, 2.99 mmol) was dissolved in Et2O (8 mL) and cooled down to −78° C. BuLi (1.3 mL, 2.5 M) was added dropwise. The resulting yellow solution was stirred at −78° C. for 45 min. 4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (720 mg, 3.61 mmol) in Et2O (5 mL) was then added dropwise. The reaction temperature rose to rt naturally overnight. H2O (10 mL) was added to quench the reaction and extracted with ethyl acetate. The combined organic layer was dried (MgSO4), filtered and concentrated. The residue was purified on silica gel column eluting with 33% to 50% ethyl acetate/hexanes to give 4-Hydroxy-4-thiazol-2-yl-piperidine-1-carboxylic acid tert-butyl ester (800 mg) as a colorless oil.

Workup

waitThe reaction temperature rose to rt naturally overnight
customto quench
customthe reaction
extractionextracted with ethyl acetate
dry with materialThe combined organic layer was dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified on silica gel column
washeluting with 33% to 50% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-973cbba951d94c548a90dc3a85682bd5
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546404B2

Reaction notes

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