Sodium hydride → Tert-butyl 10-[(4-methoxyphenyl)methyl]-9-oxo-8-phenyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylate

HRID 73042Notes

Reaction equation

HRID 73042 reaction equation
Cl[CH:2]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:3]([N:5]([CH2:15][C:16]1([OH:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:4].[H-].[Na+]>CN(C=O)C.O>[CH3:14][O:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][N:5]2[CH2:15][C:16]3([CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]3)[O:29][CH:2]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:3]2=[O:4])=[CH:12][CH:11]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 68290933Tert-butyl 4-[[(2-chloro-2-phenyl-acetyl)-[(4-methoxyphenyl)methyl]amino]methyl]-4-hydroxy-piperidine-1-carboxylate

Product 1

HCID 70872946Tert-butyl 10-[(4-methoxyphenyl)methyl]-9-oxo-8-phenyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylateYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of tert-butyl 4-[[(2-chloro-2-phenyl-acetyl)-[(4-methoxyphenyl)methyl]amino]methyl]-4-hydroxy-piperidine-1-carboxylate (322 mg, 0.64 mmol) in DMF (3 mL) at 0° C. was added NaH (27 mg, 0.67 mmol). The reaction mixture was allowed to warm to room temperature overnight, then diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography using 0-40% EtOAc/DCM to give tert-butyl 10-[(4-methoxyphenyl)methyl]-9-oxo-8-phenyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylate (215 mg, 72%) as a colorless oil. ESI-MS m/z calc. 502.2. Found 503.5 (M+1)+; Retention time: 1.90 minutes (3 min run).

Workup

  1. extractionextracted with ethyl acetate (3×15 mL)
  2. washThe combined organic layers were washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-205b3d684be049038b1fa5c11a6c38a9
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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