Sodium hydride → Benzyl [(9S)-11-oxo-9-phenyl-6,10-diazaspiro[4.6]undec-10-yl]acetate

HRID 1864936Notes

Reaction equation

HRID 1864936 reaction equation
[H-].[Na+].[C:3]1([C@H:9]2[NH:19][C:18](=[O:20])[C:13]3([CH2:17][CH2:16][CH2:15][CH2:14]3)[NH:12][CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>C1COCC1>[O:20]=[C:18]1[C:13]2([CH2:17][CH2:16][CH2:15][CH2:14]2)[NH:12][CH2:11][CH2:10][C@@H:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:19]1[CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 62576Benzyl bromoacetateHCID 66973323(9S)-9-phenyl-6,10-diazaspiro[4.6]undecan-11-one

Product 1

HCID 86616407Benzyl [(9S)-11-oxo-9-phenyl-6,10-diazaspiro[4.6]undec-10-yl]acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (0.147 g, 6.14 mmol) in THF (10 mL) was added (9S)-9-phenyl-6,10-diazaspiro[4.6]undecan-11-one (0.300 g, 1.23 mmol) at ambient temperature. The reaction was warmed to 60° C. for 2 h, then cooled to ambient temperature. Benzyl bromoacetate (0.309 g, 1.35 mmol) was added dropwise to the reaction. After 1 h, the mixture was quenched with a saturated aqueous ammonium chloride solution. The mixture was concentrated in vacuo then partitioned between H2O and CH2Cl2. The aqueous phase was then extracted several times with CH2Cl2. The combined organic extracts were washed with saturated brine, then dried over MgSO4, filtered and concentrated in vacuo The residue was purified by silica gel chromatography, eluting with a gradient of EtOAc:hexane-0:100 to 100:0, to yield the title compound. MS: m/z=393 (M+1).

Workup

  1. temperaturecooled to ambient temperature
  2. customthe mixture was quenched with a saturated aqueous ammonium chloride solution
  3. concentrationThe mixture was concentrated in vacuo
  4. customthen partitioned between H2O and CH2Cl2
  5. extractionThe aqueous phase was then extracted several times with CH2Cl2
  6. washThe combined organic extracts were washed with saturated brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo The residue
  10. customwas purified by silica gel chromatography
  11. washeluting with a gradient of EtOAc

Sources & evidence

ORD record
ord-33e166f6158a4efd93be5e402930f1b5
Source dataset
uspto-grants-2009_12
Patent number
US07625901B2

Reaction notes

Loading…