Water → Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate

HRID 1691650Notes

Reaction equation

C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:11][CH2:12][O:13][C:14]([CH3:16])=[O:15].[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].O>C1COCC1>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([CH2:16][C:14]([O:13][CH2:12][CH3:11])=[O:15])([OH:30])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: -70 °C

Procedure

A 1.0 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (40 mL, 40 mmol) was cooled to −70° C. under a nitrogen atmosphere. EtOAc (3.91 mL, 40 mmol) was slowly added dropwise thereto. The reaction mixture was stirred for 10 min at −70° C. stirred and a solution of 1-(tert-butyloxycarbonyl)-4-piperidone (7.34 g, 36.84 mmol, Lancaster, order number: 13361) in THF (16 mL) was slowly added dropwise thereto. After heating the reaction solution to 0° C., water (50 mL) was added and the reaction mixture repeatedly extracted with ether. The combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. 11.31 g of the desired product 4-ethoxycarbonylmethyl-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (A1) were obtained and further reacted without purification.

Workup

stirringstirred
temperatureAfter heating the reaction solution to 0° C.
extractionthe reaction mixture repeatedly extracted with ether
washThe combined organic phases were washed with sat. aq. NaCl solution
dry with materialdried over Na2SO4
customthe solvent was removed under a vacuum

Sources & evidence

ORD record: ord-17caec5a4675453da0f13142ccaad8b3
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153795B2

Reaction notes

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