Tetrabutylammonium Fluoride → tert-butyl tert-butoxycarbonyl(4-((3R,4R,5S)-3-((tert-butoxycarbonyl)amino)-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)carbamate

HRID 879182Notes

Reaction equation

HRID 879182 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[N:22]1[CH2:27][C@H:26]([CH3:28])[C@@H:25]([O:29][Si](C(C)(C)C)(C)C)[C@H:24]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:23]1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[N:22]1[CH2:27][C@H:26]([CH3:28])[C@@H:25]([OH:29])[C@H:24]([NH:37][C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:23]1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86705227tert-butyl tert-butoxycarbonyl(4-((3R,4R,5S)-3-((tert-butoxycarbonyl)amino)-4-((tert-butyldimethylsilyl)oxy)-5-methylpiperidin-1-yl)pyridin-3-yl)carbamate

Product 1

HCID 86705228tert-butyl tert-butoxycarbonyl(4-((3R,4R,5S)-3-((tert-butoxycarbonyl)amino)-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)carbamateYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl tert-butoxycarbonyl(4-((3R,4R,5S)-3-((tert-butoxycarbonyl)amino)-4-((tert-butyldimethylsilyl)oxy)-5-methylpiperidin-1-yl)pyridin-3-yl)carbamate (1.0 equiv.) in THF (0.20 M) at RT was added TBAF (1.0 equiv.). The resulting mixture was stirred at rt for 4 hrs. The reaction mixture was then diluted with EtOAc and water. The organic layer was washed with Brine, dried over MgSO4, concentrated and purified by flash column chromatography to yield tert-butyl tert-butoxycarbonyl(4-((3R,4R,5S)-3-((tert-butoxycarbonyl)amino)-4-hydroxy-5-methylpiperidin-1-yl)pyridin-3-yl)carbamate in 87% yield. LC/MS (m/z)=523.4 (MH+), Rt=0.72 min. 1H NMR (400 MHz, <cdcl3>) δ ppm 1.03 (d, J=6.65 Hz, 3H), 1.34-1.51 (m, 54H), 1.72-1.87 (m, 1H), 2.05 (s, 1H), 2.46-2.57 (m, 1H), 2.69 (t, J=11.35 Hz, 1H), 2.78-2.94 (m, 1H), 3.00-3.14 (m, 1H), 3.45 (d, J=12.52 Hz, 1H), 3.53-3.76 (m, 1H), 4.63 (d, J=6.26 Hz, 1H), 6.88 (d, J=5.48 Hz, 3H), 8.13 (s, 3H), 8.26-8.36 (m, 3H).

Workup

  1. washThe organic layer was washed with Brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-4c635b8fa96042449f9a036b39c10ae6
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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