Tert-butyl 4-cyano-4-(5-methylisoxazol-3-yl)piperidine-1-carboxylate → Tert-butyl 4-(aminomethyl)-4-(5-methylisoxazol-3-yl)piperidine-1-carboxylate

HRID 1800828Notes

Reaction equation

HRID 1800828 reaction equation
[C:1]([C:3]1([C:16]2[CH:20]=[C:19]([CH3:21])[O:18][N:17]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]>ClCCl>[NH2:2][CH2:1][C:3]1([C:16]2[CH:20]=[C:19]([CH3:21])[O:18][N:17]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

3

Reactant 1

HCID 59321405Tert-butyl 4-cyano-4-(5-methylisoxazol-3-yl)piperidine-1-carboxylate

Product 1

HCID 59321378Tert-butyl 4-(aminomethyl)-4-(5-methylisoxazol-3-yl)piperidine-1-carboxylateYield 107%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

470 mg tert-butyl 4-cyano-4-(5-methylisoxazol-3-yl)piperidine-1-carboxylate and 1.24 g Bu4NBH4 were dissolved in 10 ml dichloromethane in a sealed tube and heated in a microwave reactor to 80 C for 1 hour. The reaction mixture was cooled to room temperature, the vial opened and the excess borohydride was quenched by slow addition of 5 ml MeOH. After stirring for 1 hour the vial was re-sealed and heated to 100 C. for 20 minutes (to hydrolyse the boron complex of the product). The reaction mixture was poured into sat. aq. NaHCO3 solution and extracted with dichloromethane. The organic layer was washed with brine, dryed over MgSO4, filtered and concentrated. The crude title amine (0.51 g, quant. yield) was used “as is”.

Workup

  1. temperatureheated in a microwave reactor to 80 C for 1 hour
  2. customthe excess borohydride was quenched by slow addition of 5 ml MeOH
  3. customwas re-sealed
  4. temperatureheated to 100 C
  5. waitfor 20 minutes (to hydrolyse
  6. additionThe reaction mixture was poured into sat. aq. NaHCO3 solution
  7. extractionextracted with dichloromethane
  8. washThe organic layer was washed with brine
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-668025bc405c462b933a67341df2ef08
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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