Sodium borohydride → 4-(2-Cyano-1-hydroxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

HRID 1986183Notes

Reaction equation

HRID 1986183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15](=[O:19])[CH2:16][C:17]#[N:18])([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([OH:19])[CH2:16][C:17]#[N:18])([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 688570574-(2-Cyanoacetyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 688591354-(2-Cyano-1-hydroxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 4-(2-cyanoacetyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester (6.20 g, 23.3 mmol) dissolved in dry MeOH (95 mL) is added sodium borohydride (1.76 g, 46.6 mmol) portion wise over 10 minutes. The ice bath is removed after 1 hour and stirring is continued for 1 hour. The reaction mixture is concentrated, then dissolved in EtOAc (50 mL) and some MeOH. The mixture is washed with 1N HCl (25 mL). Saturated aqueous sodium chloride (25 mL) is added and the organic layer is dried over Na2SO4, then concentrated. The residue is dissolved in dichloromethane, loaded onto a silica gel column, and chromatographed. After pooling fractions and concentrating, the mixture is dissolved in MeOH and concentrated again to give the title compound as a slightly yellow oil (5.89 g, 95% yield).

Workup

  1. customThe ice bath is removed after 1 hour
  2. concentrationThe reaction mixture is concentrated
  3. dissolutiondissolved in EtOAc (50 mL)
  4. washThe mixture is washed with 1N HCl (25 mL)
  5. additionSaturated aqueous sodium chloride (25 mL) is added
  6. dry with materialthe organic layer is dried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe residue is dissolved in dichloromethane
  9. customchromatographed
  10. concentrationconcentrating
  11. dissolutionthe mixture is dissolved in MeOH
  12. concentrationconcentrated again

Sources & evidence

ORD record
ord-8a9cfb19da0b46bda20e951c7f82ecff
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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