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

HRID 2194126노트

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HRID 2194126 반응식
[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]

참가 물질

5

반응물 3

HCID 11534BromoacetonitrileHCID 2724682Lithium diisopropylamideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

생성물 1

HCID 533020741-tert-Butyl 4-ethyl 4-(cyanomethyl)piperidine-1,4-dicarboxylate수율 125.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-5 °C

실험 절차

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+].

후처리

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

출처 및 근거

ORD 기록
ord-972701f6f34649c9bea4047b3eb32799
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329904B2

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