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 924501Notes

Reaction equation

HRID 924501 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([O:15][Si](C(C)(C)C)(C)C)[C@@H:13]([CH3:23])[CH2:12][N:11]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[N:30]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.CCOC(C)=O.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([OH:15])[C@@H:13]([CH3:23])[CH2:12][N:11]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[N:30]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

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 93.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of di-tert-butyl [4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]imidodicarbonate (1.01 g, 1.58 mmol) in THF (7.9 mL) at room temperature 1.0 M tetra-n-butylammonium fluoride in THF (1.66 mL, 1.66 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was then diluted with EtOAc and water and the layers were separated. The organic layer was washed with brine, dried, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica using CombiFlash® apparatus (0 to 80% EtOAc in hexanes) to give the sub-title compound (771 mg, 93%). LCMS calc. for C26H43N4O7 (M+H)+: m/z=523.3. Found: 523.2.

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on silica using CombiFlash® apparatus (0 to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f8b3fb6709da4b27a2065589418220c4
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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