Sodium hydride → Tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate

HRID 1036725Notes

Reaction equation

HRID 1036725 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[C:11](=[O:25])[NH:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:29][C:30]1[CH:34]=[C:33]([CH3:35])[O:32][N:31]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:13]3)[C:11](=[O:25])[N:10]([CH2:29][C:30]3[CH:34]=[C:33]([CH3:35])[O:32][N:31]=3)[CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27763043-(Bromomethyl)-5-methylisoxazoleHCID 71060587HCID 71060587, compound

Product 1

HCID 71060659Tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Tert-butyl 4-(4-fluorophenyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate (200 mg; 0.574 mmol) was solubilised in DMF (5 ml) and cooled to 0° C. 60% Sodium hydride dispersion in mineral oil (46 mg, 1.148 mmol) was added and the mixture stirred at 0° C. for 45 minutes. 3-(Bromomethyl)-5-methylisoxazole (101 mg; 0.574 mmol) was solubilised in DMF (0.7 ml) and added. The reaction was stirred at 0° C. for 30 minutes then warmed to RT for 3 hr. The mixture was quenched with water and extracted with EtOAc. The organics were combined and washed with brine and dried over magnesium sulphate, filtered and concentrated in vacuo. The resultant oil was purified by chromatography on silica eluting with 50-100% TBME in iso-hexane to yield tert-butyl 4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)methyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate.

Workup

  1. additionadded
  2. stirringThe reaction was stirred at 0° C. for 30 minutes
  3. temperaturethen warmed to RT for 3 hr
  4. customThe mixture was quenched with water
  5. extractionextracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resultant oil was purified by chromatography on silica eluting with 50-100% TBME in iso-hexane

Sources & evidence

ORD record
ord-66470c6e41dc4b119b11ab847393b700
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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