Bromoacetonitrile → 1-tert-Butyl 4-ethyl 4-(cyanomethyl)piperidine-1,4-dicarboxylate

HRID 2194126Notes

Reaction equation

[Li+].[CH3:2][CH:3]([N-:5]C(C)C)C.[CH2:9]([O:11][C:12]([CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:13])[CH3:10].BrCC#N>C1COCC1>[CH2:9]([O:11][C:12]([C:14]1([CH2:2][C:3]#[N:5])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:16][CH2:15]1)=[O:13])[CH3:10]

Participants

Conditions

Temperature: -5 °C

Procedure

LDA (2M solution in THF/heptane/ethylbenzene, 97.15 ml, 0.194 mol) was added under an argon atmosphere to THF (300 ml) at −5° C., piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (25 g, 0.097 mol) in THF (100 ml) was then added dropwise and the mixture was stirred for 3 hour at −5° C. Then bromoacetonitrile (23.3 g, 0.194 mol) was added at −5° C. and the mixture was stirred overnight at RT. The solvent was evaporated off, the residue partitioned between AcOEt and water. The layers were separated, the organic layer was washed with brine, dried over sodium sulphate and then concentrated to give 4-cyanomethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (36 g) as a dark brown oil which was essentially pure and used in the next step without further purification. MS (ESI): 197.3 [(M-Boc)H+].

Workup

stirringthe mixture was stirred overnight at RT
customThe solvent was evaporated off
customthe residue partitioned between AcOEt and water
customThe layers were separated
washthe organic layer was washed with brine
dry with materialdried over sodium sulphate
concentrationconcentrated

Sources & evidence

ORD record: ord-972701f6f34649c9bea4047b3eb32799
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329904B2

Reaction notes

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