Sodium hydride → 4-(4,4-Dimethoxybutyl)-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 10181Notes

Reaction equation

HRID 10181 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14](=[O:17])[NH:13][CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:18][O:19][CH:20]([O:25][CH3:26])[CH2:21][CH2:22][CH2:23]Br>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14](=[O:17])[N:13]([CH2:23][CH2:22][CH2:21][CH:20]([O:25][CH3:26])[O:19][CH3:18])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 104202254-Bromo-1,1-dimethoxybutaneHCID 226177365-Oxo-(1,4)diazepane-1-carboxylic acid tert-butyl ester

Product 1

HCID 692244834-(4,4-Dimethoxybutyl)-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 51.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 60% sodium hydride in mineral oil (0.2 g, 5 mmole) in N,N-dimethylformamide (6 mL) was added 5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester (1.0 g, 4.67 mmole). The reaction mixture was warmed at 50° C. for 5 minutes, and then at room temperature for 15 minutes. To the resulting solution was added 4-bromobutyraldehyde dimethyl acetal (0.99 g, 5 mmole). After the reaction mixture was stirred at room temperature for 16 hours, the solvent was removed, and the residue was partitioned between water and ethyl acetate. The organic phase was washed with water, dried (magnesium sulfate), and concentrated. The residue was dissolved in diethyl ether, and the suspension was filtered, and the filtrate was concentrated. Purification by silica gel chromatography, eluting with 2% methanol in chloroform, gave 4-(4,4-dimethoxybutyl)-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.8 g,) as a heavy syrup. Nmr: (chloroform-d) δ (ppm) 1.49, s, (9H); 2.64, m, 3H; 3.32, s (3H); 4.37, m, (1H).

Workup

  1. customthe solvent was removed
  2. customthe residue was partitioned between water and ethyl acetate
  3. washThe organic phase was washed with water
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in diethyl ether
  7. filtrationthe suspension was filtered
  8. concentrationthe filtrate was concentrated
  9. customPurification by silica gel chromatography
  10. washeluting with 2% methanol in chloroform

Sources & evidence

ORD record
ord-714be3d82a8d46d68013a9111ce589f1
Source dataset
uspto-grants-2006_08
Patent number
US07094778B2

Reaction notes

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