Sodium Cyanide → tert-butyl N-[(1S,3R)-3-(cyanomethyl)cyclopentyl]carbamate

HRID 245916Notes

Reaction equation

[C-:1]#[N:2].[K+].[C-]#N.[Na+].[C:7]([O:11][C:12]([NH:14][C@@H:15]1[CH2:19][CH2:18][C@H:17]([CH2:20]OS(C)(=O)=O)[CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>CN(C=O)C>[C:7]([O:11][C:12](=[O:13])[NH:14][C@H:15]1[CH2:19][CH2:18][C@@H:17]([CH2:20][C:1]#[N:2])[CH2:16]1)([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: 80 °C

Procedure

In a round-bottomed flask, methanesulfonic acid (cis)-3-tert-butoxycarbonylamino-cyclopentylmethyl ester (crude from Step 4, 779 mg) was dissolved in DMF (5 ml). Potassium cyanide (277 mg, 4.25 mmol) was added and the reaction mixture was stirred at 80° C. overnight. Sodium cyanide (104 mg, 2.12 mmol) was added and the reaction mixture was stirred at 80° C. for 48 h. The reaction was cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc) to afford 190 mg (38%, 2 steps) of (cis-3-cyanomethyl-cyclopentyl)-carbamic acid tert-butyl ester as a light yellow oil.

Workup

stirringthe reaction mixture was stirred at 80° C. for 48 h
temperatureThe reaction was cooled to room temperature
customquenched with water
extractionextracted with diethyl ether (2×)
washThe combined organic layers were washed twice with water and once with brine
dry with materialthen dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc)

Sources & evidence

ORD record: ord-76c9e5024f61495c9332d39627a483d1
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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