Hydrochloric Acid → Benzyl 4-amino-4-cyanopiperidine-1-carboxylate

HRID 597836Notes

Reaction equation

HRID 597836 reaction equation
[OH-].[NH4+:2].[CH2:3]([O:10][C:11]([N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[NH4+:21].[C-:22]#N.[Na+].Cl>CO>[NH2:2][C:16]1([C:22]#[N:21])[CH2:17][CH2:18][N:13]([C:11]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:12])[CH2:14][CH2:15]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8929Sodium CyanideHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 53217057Benzyl 4-amino-4-cyanopiperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred mixture of ammonium hydroxide (856 mL), 1-(benzyloxycarbonyl)-4-piperidinone (1.07 mol) and ammonium chloride (113.42 g, 2.14 mol) in methanol (350 mL) was added sodium cyanide (105 g, 2.14 mmol) and stirred at room temperature for 36 h. The mixture was extracted with CH2Cl2 two times. The organic phases were combined and dried (Na2SO4) and concentrated. The pale yellow oil was dissolved in CH2Cl2 and ethereal HCl was added (699 mL, 1.4 mol, 2 M solution). The resulting white suspension was stirred at room temp 18 h. The solid was collected by filtration to give the title compound as white solid (314.5 g, 100% yield). 1H NMR (300 MHz, CDCl3) δ: 7.33-7.27 (5H, m), 5.10 (2H, s), 4.00-3.97 (2H, m), 3.25 (2H, td, J=12.2, 2.8 Hz), 1.97-1.93 (2H, m), 1.78 (2H, s), 1.65-1.59 (2H, m).

Workup

  1. extractionThe mixture was extracted with CH2Cl2 two times
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. dissolutionThe pale yellow oil was dissolved in CH2Cl2
  5. stirringThe resulting white suspension was stirred at room temp 18 h
  6. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-86c0ef266dca43789c6012f6f0566840
Source dataset
uspto-grants-2011_03
Patent number
US07897593B2

Reaction notes

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