Sodium Cyanide → tert-butyl ((3S,4S,5R)-1-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-4-cyano-5-methylpiperidin-3-yl)carbamate

HRID 879224

Reaction equation

[C:1]([O:5][C:6]([N:8](C(OC(C)(C)C)=O)[C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[N:15]1[CH2:20][C@@H:19]([CH3:21])[C@@H:18]([CH2:22]S([O-])(=O)=O)[C@@H:17]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C-]#[N:43].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[N:15]1[CH2:20][C@H:19]([CH3:21])[C@H:18]([C:22]#[N:43])[C@H:17]([NH:27][C:28](=[O:29])[O:30][C:31]([CH3:33])([CH3:34])[CH3:32])[CH2:16]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (3R,4R,5S)-1-(3-(bis(tert-butoxycarbonyl)amino)pyridin-4-yl)-3-(tert-butoxycarbonylamino)-5-methylpiperidin-4-ylmethanesulfonate (1.0 equiv.) in DMF (0.10 M) was added NaCN (5.0 equiv.). The mixture was stirred at 80° C. for 6 hrs and partitioned between EtOAc and H2O. The organic layer was washed NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield tert-butyl ((3S,4S,5R)-1-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-4-cyano-5-methylpiperidin-3-yl)carbamate in 5% yield. LC/MS (m/z)=432.2 (MH+), Rt=0.73 min.

Workup

custompartitioned between EtOAc and H2O
washThe organic layer was washed NaCl(sat.)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
custompurified by ISCO SiO2 chromatography

Sources & evidence

ORD record: ord-aec89d1b74fc443dab9c9ff2ba2a9344
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987457B2

Linked notes

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