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 705310Notes

Reaction equation

HRID 705310 reaction equation
CS(O[C@@H:6]1[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[N:19]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:8][C@H:7]1[NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])(=O)=O.[N-:42]=[N+:43]=[N-:44].[Na+]>CN(C=O)C>[N:42]([C@H:6]1[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[N:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:27](=[O:28])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:8][C@H:7]1[NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[N+:43]=[N-:44]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 86705229(3R,4R,5S)-1-(3-(bis(tert-butoxycarbonyl)amino)pyridin-4-yl)-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-4-yl methanesulfonate

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-yl methanesulfonate (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, 3 H), 1.33-1.52 (m, 30 H), 2.03-2.19 (m, 1 H), 2.66-2.87 (m, 2 H), 3.16 (dd, J=12.72, 2.15 Hz, 1 H), 3.22-3.32 (m, 1 H), 3.81-4.01 (m, 2 H), 4.78 (d, J=9.00 Hz, 1 H), 6.76-6.88 (m, 1 H), 8.05-8.18 (m, 1 H), 8.26-8.37 (m, 1 H).

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-7c1de90e72aa46ca8a461670172b17d0
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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