Sodium hydride → (Rac)-4-[3-(tert-butyl-dimethyl-silanyloxy)-1-methoxycarbonyl-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester

HRID 655503Notes

Reaction equation

HRID 655503 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:21][O:22][C:23](=[O:36])[CH:24](I)[CH2:25][CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].S([O-])(O)(=O)=O.[K+]>CN(C)C=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][C:15](=[O:18])[N:14]([CH:24]([C:23]([O:22][CH3:21])=[O:36])[CH2:25][CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 27602541-Cbz-[1,4]diazepan-5-oneHCID 87149689(Rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester2×

Product 1

HCID 67080917(Rac)-4-[3-(tert-butyl-dimethyl-silanyloxy)-1-methoxycarbonyl-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid benzyl esterYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6.95 g (28.0 mmol) of 5-oxo-[1,4]diazepane-1-carboxylic acid benzyl ester in 85 ml of N,N-dimethylformamide was treated at 0° C. with 1.47 g (33.6 mmol) of NaH (55% in oil) in three portions. After 30 min, 10.0 g (28.0 mmol) of (rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester (intermediate 1) were added during 5 min. The solution was stirred 2¼ h at 0° C. and neutralized with cold 10% aq. potassium hydrogensulfate solution and extracted with diethyl ether (3×). The organic phases were washed with sat. aq. sodium hydrogencarbonate solution, 10% aq. sodium chloride solution, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane/ethyl acetate 4:1 to 2:1) to yield 8.45 g (63%) of the title compound as yellow viscous oil. MS: 479.2 (MH+).

Workup

  1. extractionextracted with diethyl ether (3×)
  2. washThe organic phases were washed with sat. aq. sodium hydrogencarbonate solution, 10% aq. sodium chloride solution
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. custompurified by flash silica gel column (n-heptane/ethyl acetate 4:1 to 2:1)

Sources & evidence

ORD record
ord-14c84dc3398247f383efd89c26b9e42c
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

Loading…