Sodium Hydroxide → Tert-butyl 4-(aminomethyl)-4-(cyclopropylmethyl)piperidine-1-carboxylate

HRID 551140Notes

Reaction equation

HRID 551140 reaction equation
[C:1]([C:3]1([CH2:16][CH:17]2[CH2:19][CH2:18]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].[OH-].[Na+]>C(O)C.C(O)C.O>[NH2:2][CH2:1][C:3]1([CH2:16][CH:17]2[CH2:19][CH2:18]2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[CH2:5][CH2:4]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 57425738Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

Product 1

HCID 57425745Tert-butyl 4-(aminomethyl)-4-(cyclopropylmethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 19096565Water ethanolSolvent

Procedure

A solution of the tert-butyl 4-cyano-4-cyclopropylmethylpiperidine-1-carboxylate (I-2) (1.00 g, 3.78 mmol) in ethanol (5 mL) was added to 1M sodium hydroxide in 95% ethanol-water (75 mL) and the solution degassed with nitrogen. Raney Nickel (50% slurry in water) (2.6 g) was added and the black suspension shaken under hydrogen pressure (40 psi) at room temperature for 12 h. The catalyst was filtered off and washed with 95% ethanol-water. The filtrate was evaporated in vacuo then partitioned between water and DCM. The organic phase was separated and the aqueous phase re-extracted with DCM twice. The combined organic phase was dried (MgSO4) and the solvent removed in vacuo to leave tert-butyl 4-aminomethyl-4-cyclopropylmethylpiperidine-1-carboxylate (I-3) that was used in the next step without further purification. 1H NMR (500 MHz, CDCl3): δ 3.44 (m, 2H), 3.32 (m, 2H), 2.71 (s, 2H), 1.41 (s, 9H), 1.46-1.38 (m, 4H), 1.28 (d, J=6.7, 2H), 1.46 (s, 9H), 0.60 (m, 1H), 0.46 (m, 2H), 0.05 (m, 2H).

Workup

  1. customthe solution degassed with nitrogen
  2. additionRaney Nickel (50% slurry in water) (2.6 g) was added
  3. filtrationThe catalyst was filtered off
  4. washwashed with 95% ethanol-water
  5. customThe filtrate was evaporated in vacuo
  6. customthen partitioned between water and DCM
  7. customThe organic phase was separated
  8. extractionthe aqueous phase re-extracted with DCM twice
  9. dry with materialThe combined organic phase was dried (MgSO4)
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-1ecdf9b7949546eaac52e0bc34f55085
Source dataset
uspto-grants-2011_05
Patent number
US07947714B2

Reaction notes

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