Sodium Bromate → tert-butyl[(5S)-5-[(tert-butoxycarbonyl)amino]-6-{[tert-butyl(diphenyl)silyl]oxy}hexanoyl]carbamate

HRID 1524344Notes

Reaction equation

HRID 1524344 reaction equation
[C:1]([O:5][C:6](=[O:40])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C@H:12]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].Br([O-])(=O)=[O:42].[Na+]>CCOC(C)=O.O.O.[Ru]=O>[C:1]([O:5][C:6](=[O:40])[NH:7][C:8](=[O:42])[CH2:9][CH2:10][CH2:11][C@H:12]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:13][O:14][Si:15]([C:28]([CH3:30])([CH3:31])[CH3:29])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 23668195Sodium Bromate2×HCID 89938446tert-butyl[(5S)-5-[(tert-butoxycarbonyl)amino]-6-{[tert-butyl(diphenyl)silyl]oxy}hexyl]carbamate

Product 1

HCID 89938443tert-butyl[(5S)-5-[(tert-butoxycarbonyl)amino]-6-{[tert-butyl(diphenyl)silyl]oxy}hexanoyl]carbamateYield 36.8%

Reagents, catalysts & solvents 3

HCID 178526987HCID 178526987, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the material from Step 2 (339.5 g, 595 mmol) in EtOAc (1000 mL) and H2O (1400 mL) at room temperature were added sodium bromate (250 g, 1657 mmol) and ruthenium oxide hydrate (3 g, 19.86 mmol). The reaction mixture was stirred at room temperature overnight, 50% of conversion. The mixture was then heated at 55° C. overnight. Additional sodium bromate (100 g) was added and the resulting mixture was heated at 40° C. for 12 hours. Upon cooling to room temperature, the reaction mixture was filtered through celite. The filtrate was extracted with EtOAc (2×). The combined organics were then washed with aqueous sodium bisulfite and brine, and dried over MgSO4. The filtrate was treated with charcoal (Darco® G-60, Norit Americas Inc., Marshall, Tex.) and filtered through a pad of silica gel. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography on silica gel using EtOAc-hexanes to yield 128 g of the title compound as a colorless viscous oil. 1H NMR (CHCl3-d): δ 7.67-7.62 (m, 4H), 7.58-7.52 (b, 1H), 7.42-7.35 (m, 6H), 4.72-4.65 (b, 1H), 3.70-3.62 (m, 2H), 3.58-3.52 (m, 1H), 2.76-2.62 (m, 2H), 1.75-1.55 (m, 2H), 1.48 (s, 9H), 1.42 (s, 9H), 1.32-1.23 (m, 2H), 1.05 (s, 9H).

Workup

  1. temperatureThe mixture was then heated at 55° C. overnight
  2. temperaturethe resulting mixture was heated at 40° C. for 12 hours
  3. temperatureUpon cooling to room temperature
  4. filtrationthe reaction mixture was filtered through celite
  5. extractionThe filtrate was extracted with EtOAc (2×)
  6. washThe combined organics were then washed with aqueous sodium bisulfite and brine
  7. dry with materialdried over MgSO4
  8. additionThe filtrate was treated with charcoal (Darco® G-60, Norit Americas Inc., Marshall, Tex.)
  9. filtrationfiltered through a pad of silica gel
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-beeb3631bbca49f1bf462552d27f2610
Source dataset
uspto-grants-2015_07
Patent number
US09079834B2

Reaction notes

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