Benzyl Bromide → HCID 18373992, compound

HRID 619325Notes

Reaction equation

HRID 619325 reaction equation
[NH2:1][C:2]1([C:12]([OH:14])=[O:13])[CH2:7][CH:6]([OH:8])[CH:5]2[CH:3]1[CH:4]2[C:9]([OH:11])=[O:10].[C-]#N.[K+].C([O-])(O)=O.[Na+].C(Br)C1C=CC=CC=1>CCO.O.CCOC(C)=O>[NH2:1][C:2]1([C:12]([OH:14])=[O:13])[CH2:7][C:6](=[O:8])[CH:5]2[CH:3]1[CH:4]2[C:9]([OH:11])=[O:10]

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 9032Potassium CyanideHCID 516892Sodium BicarbonateHCID 22119095HCID 22119095, compound

Product 1

HCID 18373992HCID 18373992, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
40 °C

Procedure

(1S*, 2S*, 4S*, 5R*, 6R*)-Ethyl 2-(3'-benzyl-5'-spirohydantoin)-4-hydroxybicyclo[3.1.0]hexane-6-carboxylate. To a stirred solution of the product of Example 1, step (c) (14.5 g, 78.7 mmol) in EtOH/H2O (2:1) (150 mL total volume) was added NH2CO2NH4 (18.42 g, 236 mmol) then KCN (7.68 g, 118 mmol). Upon complete addition, the reaction mixture was warmed at 40° C. for 2 days. The reaction mixture was concentrated in vacuo, partitioned with EtOAc/1N HCl, and brine. The mixture of hydantoins was extracted with EtOAc, dried over MgSO4, and concentrated. The crude hydantoins were reconstituted in DMF (50 mL) and stirred at room temperature as NaHCO3 (16.85 g, 200 mmol) and then benzyl bromide (12.6 g, 73.5 mmol) were consecutively added. The reaction mixture was warmed at 100° C. overnight. The reaction mixture was diluted with EtOAc and partitioned with 0.5N HCl. The hydantoins were extracted with EtOAC, washed with H2O then brine, dried over MgSO4, and purified via HPLC (hexanes/EtOAc) to afford 5.14 g (19%, 14.9 mmol) of the title compound. FDMS: M+ =344. Anal. calcd. for C18H20N2O5 : C, 62.78; H, 5.85; N, 8.13. Found: C, 62.97; H, 5.97; N, 8.06.

Workup

  1. additionUpon complete addition
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompartitioned with EtOAc/1N HCl, and brine
  4. additionThe mixture of hydantoins
  5. extractionwas extracted with EtOAc
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. temperatureThe reaction mixture was warmed at 100° C. overnight
  9. custompartitioned with 0.5N HCl
  10. extractionThe hydantoins were extracted with EtOAC
  11. washwashed with H2O
  12. dry with materialbrine, dried over MgSO4
  13. custompurified via HPLC (hexanes/EtOAc)

Sources & evidence

ORD record
ord-c3ea64e138ae4e089882596538942f93
Source dataset
uspto-grants-1999_09
Patent number
US05958960

Reaction notes

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