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

HRID 879226

Reaction equation

HRID 879226 reaction equation
[C:1]([O:5][C:6]([N:8]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[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](CS([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].[N-:42]=[N+:43]=[N-:44].[Na+]>CN(C=O)C>[N:42]([C@H:18]1[C@@H:19]([CH3:21])[CH2:20][N:15]([C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:8]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH2:16][C@H:17]1[NH:27][C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])=[N+:43]=[N-:44]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 86705277(3R,4R,5S)-1-(3-(bis(tert-butoxycarbonyl)amino)pyridin-4-yl)-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-4-ylmethanesulfonate

Product 1

HCID 86705280tert-butyl (4-((3R,4S,5S)-4-azido-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-1-yl)pyridin-3-yl)(tert-butoxycarbonyl)carbamateYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3R,4R,5S)-1-(3-(bis(tert-butoxycarbonyl)amino)pyridin-4-yl)-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-4-ylmethanesulfonate (1.0 equiv.) in DMF (0.13 M) was added NaN3 (5.0 equiv.). The solution was submerged in an 80° C. oil bath and left stirring under Ar for 24 hrs. The solution was cooled to rt and left stirring under Ar overnight. The solution was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat.), NaCl(sat.), dried over MgSO4, filtered, concentrated to yield tert-butyl (4-((3R,4S,5S)-4-azido-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-1-yl)pyridin-3-yl)(tert-butoxycarbonyl)carbamate in 60% yield. LC/MS (m/z)=548.4 (MH+), Rt=0.94 min. 1H NMR (400 MHz, <cdcl3>) δ ppm 0.97-1.13 (m, 3H), 1.33-1.52 (m, 30H), 2.03-2.19 (m, 1H), 2.66-2.87 (m, 2H), 3.16 (dd, J=12.72, 2.15 Hz, 1H), 3.22-3.32 (m, 1H), 3.81-4.01 (m, 2H), 4.78 (d, J=9.00 Hz, 1H), 6.76-6.88 (m, 1H), 8.05-8.18 (m, 1H), 8.26-8.37 (m, 1H).

Workup

  1. customwas submerged in an 80° C.
  2. waitleft
  3. waitleft
  4. stirringstirring under Ar overnight
  5. customThe solution was partitioned between EtOAc and H2O
  6. washThe organic layer was washed with Na2CO3(sat.), NaCl(sat.)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-36f4c3c3ebb4430889b4dc4834d6094f
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Linked notes

Loading…