Water → 3-(2-Methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester

HRID 1691658Notes

Reaction equation

HRID 1691658 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:20][CH2:19][C:13]2([O:17][C:16](=[O:18])[NH:15][CH2:14]2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:21][O:22][C:23]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][C:24]=1[CH2:25]Br.O>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][C:13]2([O:17][C:16](=[O:18])[N:15]([CH2:25][C:24]3[CH:27]=[C:28]([N+:31]([O-:33])=[O:32])[CH:29]=[CH:30][C:23]=3[O:22][CH3:21])[CH2:14]2)[CH2:19][CH2:20]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 775162-(Bromomethyl)-1-methoxy-4-nitrobenzeneHCID 10015278Tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 576662783-(2-Methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl esterYield 81.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (82 mg, 60% dispersion in mineral oil, weight percent) was suspended under a nitrogen atmosphere in DMF (5 mL). Compound A3 (0.5 g, 1.95 mmol) was added thereto and the reaction mixture was stirred for 10 min at RT. 2-Methoxy-5-nitrobenzyl bromide (485 mg, 1.97 mmol) was added thereto. The reaction mixture was stirred for 18 h at RT, combined with water and extracted with EtOAc. The combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. The residue was dissolved in a mixture of ether and heptane. After removal of the ether, the desired product 3-(2-methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (A87) (670 mg, 81% of theoretical) was obtained as a white solid by filtration.

Workup

  1. stirringThe reaction mixture was stirred for 18 h at RT
  2. extractionextracted with EtOAc
  3. washThe combined organic phases were washed with sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. customthe solvent was removed under a vacuum
  6. dissolutionThe residue was dissolved in a mixture of ether and heptane
  7. customAfter removal of the ether

Sources & evidence

ORD record
ord-13846c2621284a78b6854e791a8552b1
Source dataset
uspto-grants-2012_04
Patent number
US08153795B2

Reaction notes

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