Methanol → Benzyl 4-amino-4-cyanopiperidine-1-carboxylate
Reaction equation
[C-:1]#[N:2].[Na+].[Cl-].[NH4+:5].O=[C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:9][CH2:8]1.CO>N>[CH2:16]([O:15][C:13]([N:10]1[CH2:11][CH2:12][C:7]([NH2:5])([C:1]#[N:2])[CH2:8][CH2:9]1)=[O:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1Participants
Procedure
A solution of sodium cyanide (1052 mg, 21.5 mmol), ammonium chloride (1265 mg, 23.65 mmol), and benzyl 4-oxo-1-piperidine-carboxylate (5.0 gm, 21.5 mmol), was prepared in 5 M ammonia in methanol (8.6 mL, 43 mmol). The solution was brought to reflux for 4 h and then allowed to cool to room temperature. The solution was then filtered and washed with methanol (100 mL) and the filtrate was concentrated in vacuo. The resulting oil was taken up in MTBE (250 mL) and filtered again. The filter cake was washed with MTBE (100 mL) and the filtrate was concentrated in vacuo to yield 4-amino-4-cyano-piperidine-1-carboxylic acid benzyl ester as a clear oil (3.5 g) which was used without further purification. (b) The title compound was prepared starting from N-(4-Morpholinecarbonyl)-L-cyclohexyl alanine and 4-amino-4-cyano-piperidine-1-carboxylic acid benzyl ester according to the procedure from Example 2, step b, except that the compound was purified by HPLC using a 20×250 mm C18 reverse phase column with the method being 30% acetonitrile in water to 100% acetonitrile. MS, m/z 526=M+1.
Workup
- temperatureto reflux for 4 h
- filtrationThe solution was then filtered
- washwashed with methanol (100 mL)
- concentrationthe filtrate was concentrated in vacuo
- filtrationfiltered again
- washThe filter cake was washed with MTBE (100 mL)
- concentrationthe filtrate was concentrated in vacuo
Sources & evidence
- ORD record
- ord-ec096fbb24f448af925b090d5962e700
- Source dataset
- uspto-grants-2006_06
- Patent number
- US07056915B2
Reaction notes
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