Sodium hydride → HCID 59657472, compound

HRID 494160Notes

Reaction equation

HRID 494160 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:25][CH2:24][C:14]2([O:18][C:17](=[O:19])[NH:16][CH:15]2[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH:28]1([CH2:34]Br)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][C:14]2([O:18][C:17](=[O:19])[N:16]([CH2:34][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH:15]2[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:24][CH2:25]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 137636Cyclohexane, (bromomethyl)-HCID 13016609HCID 13016609, compound

Product 1

HCID 59657472HCID 59657472, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5.0 g 4-butyl-2-oxo-1-oxa-3,8-diaza-spiro[4.5]decane-8-carboxylic acid benzyl ester (14.4 mmol) in 50 mL DMF was added 994 mg of sodium hydride (21.6 mmol, 60% dispersion in mineral oil). The reaction mixture stirred for five minutes and 2.2 mL of cyclohexylmethyl bromide (15.8 mmol) was then added. The reaction mixture stirred under nitrogen for 18 h. The reaction mixture was heated to 70° C. for three h. The reaction mixture cooled to room temperature and was diluted with 500 mL EtOAc and washed twice with water, once with brine. The organics were dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel utilizing a gradient elution (10% to 15% EtOAc/DCM) to provide 4.1 g (65%) of 4-butyl-3-cyclohexylmethyl-2-oxo-1-oxa-3,8-diaza-spiro[4.5]decane-8-carboxylic acid benzyl ester: ms [M]+=443.

Workup

  1. stirringThe reaction mixture stirred under nitrogen for 18 h
  2. temperatureThe reaction mixture cooled to room temperature
  3. washwashed twice with water, once with brine
  4. dry with materialThe organics were dried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel utilizing
  7. washa gradient elution (10% to 15% EtOAc/DCM)

Sources & evidence

ORD record
ord-bda7f4f6bd7a4ed1a8361b0514c2fc9d
Source dataset
uspto-grants-2009_05
Patent number
US07538122B2

Reaction notes

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