Phenylacetonitrile → Tert-butyl 4-[cyano(phenyl)methyl]-4-hydroxypiperidine-1-carboxylate

HRID 1943023Notes

Reaction equation

HRID 1943023 reaction equation
[CH2:1]([C:8]#[N:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[C:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>C1COCC1>[C:8]([CH:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:25]1([OH:28])[CH2:24][CH2:23][N:22]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:27][CH2:26]1)#[N:9]

Participants

5

Reactant 3

HCID 8794PhenylacetonitrileHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 58415929Tert-butyl 4-[cyano(phenyl)methyl]-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Benzyl cyanide (2.96 ml, 25.6 mmol) in THF (125 ml) was cooled to −78° C. nBuLi (16.17 ml, 25.9 mmol) was added dropwise over 20 min via syringe pump, and the reaction stirred for 30 min. 1-BOC-4-piperidone (5.10 g, 25.6 mmol) in THF (20 ml) was added over 20 min via syringe pump and the reaction stirred for 2.5 hours. While still cold, the reaction was quenched with satd. NH4Cl and allowed to warm overnight. The mixture was partitioned between CH2Cl2 and satd. NH4Cl, the aqueous portion extracted 3×CH2Cl2, and the organic portion dried (Na2SO4) then concentrated in vacuo. The resulting material was carried on without further purification.

Workup

  1. additionwas added dropwise over 20 min via syringe pump
  2. stirringthe reaction stirred for 2.5 hours
  3. customWhile still cold, the reaction was quenched with satd
  4. temperatureto warm overnight
  5. customThe mixture was partitioned between CH2Cl2 and satd
  6. extractionNH4Cl, the aqueous portion extracted 3×CH2Cl2
  7. dry with materialthe organic portion dried (Na2SO4)
  8. concentrationthen concentrated in vacuo
  9. customThe resulting material was carried on without further purification

Sources & evidence

ORD record
ord-4b42f9f1b02e42edb8e778476793587e
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

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