Di-tert-butyl dicarbonate → Diethylamine

HRID 1481822Notes

Reaction equation

HRID 1481822 reaction equation
[N:1]([CH:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=2[F:17])[CH2:7][N:6]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:5]1=[O:23])=[N+]=[N-].[C:24](O[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>CCO.[Pd]>[NH:6]([CH2:7][CH3:8])[CH2:5][CH3:4].[F:17][C:11]1[C:12]([F:16])=[CH:13][CH:14]=[CH:15][C:10]=1[C@@H:8]1[CH2:7][N:6]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:5](=[O:23])[C@H:4]([NH:1][C:24](=[O:25])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:9]1.[F:17][C:11]1[C:12]([F:16])=[CH:13][CH:14]=[CH:15][C:10]=1[C@H:8]1[CH2:7][N:6]([CH2:18][C:19]([F:20])([F:21])[F:22])[C:5](=[O:23])[C@@H:4]([NH:1][C:32](=[O:33])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])[CH2:9]1

Participants

7

Reactant 2

HCID 90495Di-tert-butyl dicarbonateHCID 866652043-Azido-5-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one

Product 3

HCID 8021DiethylamineHCID 86665205tert-butyl [(3R,5R)-5-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamateHCID 86665206tert-butyl[(3S,5S)-5-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a mixture of (3R,5R & 3S,5S)-3-azido-5-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one (6.14 g, 18.4 mmol) and di-tert-butyl dicarbonate (4.81 g, 22.0 mmol) in EtOH (160 mL) was added 10% palladium on carbon (0.98 g, 0.92 mmol) and the resulting mixture was stirred vigorously under an atmosphere of hydrogen (ca. 1 atm) for 18 h. The reaction mixture was filtered through a pad of Celite®, washing with EtOH, and the filtrate was concentrated in vacuo to give a crude solid. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:EtOAc—100:0 to 60:40, to give the racemic product. Separation of the enantiomers was achieved by HPLC on a ChiralPak® AD column, eluting with EtOH:hexanes:Et2NH—60:40:0.04, to give tert-butyl [(3R,5R)-5-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate as the first major peak, and tert-butyl [(3S,5S)-5-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate, the title compound, as the second major peak. MS: m/z=431.0 (M+Na).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. washwashing with EtOH
  3. concentrationthe filtrate was concentrated in vacuo
  4. customto give a crude solid
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2
  7. customEtOAc—100:0 to 60:40, to give the racemic product
  8. customSeparation of the enantiomers
  9. washeluting with EtOH

Sources & evidence

ORD record
ord-42842d71a41a4179a3cc14e4815d2703
Source dataset
uspto-grants-2016_08
Patent number
US09409916B2

Reaction notes

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