Hydrochloric Acid → 4-(2-Cyanoacetyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

HRID 1986182Notes

Reaction equation

HRID 1986182 reaction equation
[C:1](#[N:3])[CH3:2].[Li]CCCC.CO[C:11]([C:13]1([CH3:26])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)=[O:12].Cl>C1COCC1>[C:22]([O:21][C:19]([N:16]1[CH2:15][CH2:14][C:13]([C:11](=[O:12])[CH2:2][C:1]#[N:3])([CH3:26])[CH2:18][CH2:17]1)=[O:20])([CH3:23])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 463183881-tert-Butyl 4-methyl 4-methylpiperidine-1,4-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 688570574-(2-Cyanoacetyl)-4-methylpiperidine-1-carboxylic acid tert-butyl esterYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Acetonitrile (3.07 mL, 58.4 mmol) is added to THF (75 mL). At −78° C. 1.6 M BuLi in hexanes is slowly added. After 15 minutes, 4-methylpiperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (6.83 g, 26.5 mmol) dissolved in THF (75 mL) is added dropwise. After 1 hour 2.2 equivalents of 5N HCl is added at −78° C. The reaction is warmed to room temperature and concentrated to about 50 mL volume. EtOAc (50 mL) and saturated aqueous sodium chloride (25 mL) are added to the mixture. The organic layer is separated, dried over Na2SO4, concentrated, and chromatographed on silica gel, eluting with 0-20% EtOAc in dichloromethane, to give the title compound (4.80 g, 68% yield).

Workup

  1. customAt −78° C
  2. additionis added dropwise
  3. concentrationconcentrated to about 50 mL volume
  4. additionEtOAc (50 mL) and saturated aqueous sodium chloride (25 mL) are added to the mixture
  5. customThe organic layer is separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customchromatographed on silica gel
  9. washeluting with 0-20% EtOAc in dichloromethane

Sources & evidence

ORD record
ord-467e6c1a25484488a6d40072abeb8efa
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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