Sodium hydride → 4-benzyl 1,4-di-tert-butyl (1S,4S)-1-[(tert-butoxycarbonyl)amino]-5-(4-nitrophenyl)-pentane-1,4,4-tricarboxylate

HRID 591334Notes

Reaction equation

HRID 591334 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+].[N+:39]([C:42]1[CH:49]=[CH:48][C:45]([CH2:46]Br)=[CH:44][CH:43]=1)([O-:41])=[O:40]>CN(C=O)C>[C:33]([O:32][C:30]([NH:29][C@H:21]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:20][CH2:19][C@@:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:46][C:45]1[CH:48]=[CH:49][C:42]([N+:39]([O-:41])=[O:40])=[CH:43][CH:44]=1)=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 660114-Nitrobenzyl bromideHCID 117812690Di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

Product 1

HCID 1317345134-benzyl 1,4-di-tert-butyl (1S,4S)-1-[(tert-butoxycarbonyl)amino]-5-(4-nitrophenyl)-pentane-1,4,4-tricarboxylateYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate (1 g, 1.970 mmol) was dissolved in DMF (20 ml) and sodium hydride (53 mg, 1.773 mmol) was added. After stirring for 60 min, a solution of 4-nitrobenzyl bromide (426 mg, 1.970 mmol) in 10 ml DMF was added and the mixture was stirred at 60° C. for 90 min. The mixture was then concentrated in vacuo, the residue was taken up in water (50 ml) and ethyl acetate (100 ml), and the organic phase was washed with brine (3×50 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed over silica gel (hexane, ethyl acetate) to yield 1.04 g (82%) of a clear oil.

Workup

  1. stirringthe mixture was stirred at 60° C. for 90 min
  2. concentrationThe mixture was then concentrated in vacuo
  3. washethyl acetate (100 ml), and the organic phase was washed with brine (3×50 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was chromatographed over silica gel (hexane, ethyl acetate)

Sources & evidence

ORD record
ord-7a0b824b6c904727acc4a9ac19838650
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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