Sodium hydride → Di-tert-butyl (5R)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

HRID 591278Notes

Reaction equation

HRID 591278 reaction equation
[H-].[Na+].[C:3]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].Br[CH2:22][CH2:23][C@@H:24]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>CN(C)C=O>[CH2:14]([O:13][C:3]([CH:4]([CH2:22][CH2:23][C@@H:24]([NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[O:12])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2736712Benzyl tert-butyl malonateHCID 14193045(R)-4-Bromo-2-[[(tert-butoxy)carbonyl]amino]butanoic acid tert-butyl ester

Product 1

HCID 117812691Di-tert-butyl (5R)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioateYield 46.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of 66 mg sodium hydride (60% in oil, 1.66 mmol) in N,N-dimethyl-formamide (10 mL) was added a solution of 456 mg benzyl tert-butyl malonate (commercial, 1.82 mmol) in N,N-dimethylformamide (5 mL) at room temperature. The mixture was stirred for one hour at room temperature before a solution of 560 mg tert-butyl (2R)-4-bromo-2-[(tert-butoxycarbonyl)amino]butanoate (1.66 mmol) in N,N-dimethylformamide (5 mL) was added. The mixture was stirred for 60 hours at room temperature and was then evaporated in vacuo. The residue was purified by column chromatography on silica gel (1.5→20% ethyl acetate in hexane) to give the title compound (390 mg, 46% yield).

Workup

  1. additionwas added
  2. customwas then evaporated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (1.5→20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c8eacce7d299466e870aa1ce0f7d5e08
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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