Diisopropylamine → tert-Butyl 3-(2-tert-butoxy-2-oxoethyl)-4-oxopiperidine-1-carboxylate

HRID 1673197Notes

Reaction equation

C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Br[CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C.[NH4+].[Cl-].CC(=O)OCC>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][C:23](=[O:26])[CH:24]([CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of diisopropylamine (13.5 ml, 96 mmol) in THF (300 ml) at −78° C. was added dropwise n-BuLi (2.5M in Hex, 32 ml). The mixture was warmed to −10° C. and re-cooled to −78° C. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (10 g, 50 mmol) in THF (50 ml) was then added dropwise and the mixture stirred at −78° C. for another 15 min. A solution of tert-butyl bromoacetate (12.6 ml, 85 mmol) in THF (30 ml) and HMPT (5 ml) was then added dropwise and the mixture stirred at −78° C. for 4 h and then gradually warmed to rt. The mixture was taken up in sat. aq. NH4Cl and extracted with EA. The yield after work up and chromatography (eluent Hex/EA 4:1) was 7.6 g (50.6%; yellowish oil).

Workup

temperaturere-cooled to −78° C
stirringthe mixture stirred at −78° C. for 4 h
temperaturegradually warmed to rt
extractionextracted with EA
customThe yield after work up

Sources & evidence

ORD record: ord-4c90b927952845cdabd843c3059acadf
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999115B2

Reaction notes

Loading…