Benzyl Bromide → (1S,2S,5R,6R)-2-amino-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid

Temperature

40 °C

(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 NaHCO1 (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 0.5 N 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.

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 0.5 N 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)

ORD record

ord-f1b0ce242dc04763a2c081fbc4efa969

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06268507B1