Sodium hydride → di-tert-butyl (5S)-2-[4-(benzyloxy)benzyl]-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

HRID 591273Notes

Reaction equation

HRID 591273 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([CH2:19][CH2:20][C@H:21]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:39]([O:46][C:47]1[CH:54]=[CH:53][C:50]([CH2:51]Br)=[CH:49][CH:48]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CN(C)C=O>[CH2:39]([O:46][C:47]1[CH:48]=[CH:49][C:50]([CH2:51][C:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])([CH2:19][CH2:20][C@H:21]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:53][CH:54]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 104927561-(Benzyloxy)-4-(bromomethyl)benzeneHCID 117812690Di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

Product 1

HCID 70977725di-tert-butyl (5S)-2-[4-(benzyloxy)benzyl]-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1.00 g di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)-amino]hexanedioate (1.97 mmol) in NA-dimethyl formamide (20 mL) was added under argon atmosphere 71 mg of sodium hydride (60% in oil, 1.77 mmol). The resulting mixture was stirred at room temperature for 30 minutes. A solution of 546 mg 4-benzyloxybenzyl bromide (1.97 mmol; prepared according to Helv. Chim. Acta, 2002, 85, 3422) in N,N-dimethylformamide (10 mL) was added, and the mixture was stirred at 60° C. for one hour. After cooling to room temperature, the mixture was concentrated in vacuo and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel (2.5→20% ethyl acetate in hexane) to give 1.22 g of the title compound (88% yield).

Workup

  1. stirringthe mixture was stirred at 60° C. for one hour
  2. temperatureAfter cooling to room temperature
  3. concentrationthe mixture was concentrated in vacuo
  4. custompartitioned between water and ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica gel (2.5→20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2222bfd403bd45fd8874dacab2933db2
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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