Citric Acid → 8-Tert-butoxycarbonyl-3-benzyl-1-(4-fluoro-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]decane

HRID 1683047Notes

Reaction equation

HRID 1683047 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][C:11]2([N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH2:14][NH:13][C:12]2=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2([N:15]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[CH2:14][N:13]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:12]2=[O:23])[CH2:24][CH2:25]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 311Citric Acid2×HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 53951483HCID 53951483, compound

Product 1

HCID 541984368-Tert-butoxycarbonyl-3-benzyl-1-(4-fluoro-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]decane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine 8-tert-butoxycarbonyl-1-(4-fluoro-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]decane (12 mmol) and DMF (20 mL). Cool in an ice bath. Add NaH (18 mmol) in several portions. After the addition is complete, add benzyl bromide (18 mmol). Allow the reaction mixture to warm to ambient temperature. After 3 h, cool the reaction vessel using an ice bath and cautiously add 10% aqueous citric acid (20 mL). When gas evolution has ceased, pour into an additional 20 mL of 10% aqueous citric acid and extract using ethyl acetate (3×60 mL). Extract the combined organics with saturated aqueous NaCl, dry over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Purify to obtain the title compound.

Workup

  1. temperatureCool in an ice bath
  2. additionAfter the addition
  3. temperaturecool the reaction vessel
  4. extractionextract
  5. extractionExtract the combined organics with saturated aqueous NaCl
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto obtain a residue
  10. customPurify

Sources & evidence

ORD record
ord-0e6f582089fe43bfa4e086caf337448a
Source dataset
uspto-grants-1997_06
Patent number
US05635510

Reaction notes

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