Ethyl bromoacetate → trans-4-benzylhexahydrocyclopenta[b][1,4]oxazin-3(2H)-one

Temperature

0 °C

To a suspension of NaH (6.0 g of 60% w/w in oil, 150 mmol) in THF (300 mL) cooled at 0° C., trans-2-(benzylamino)cyclopentanol (9.6 g, 50 mmol) was added slowly. After stirring for 15 minutes at 0° C., ethyl bromoacetate (10 g, 60 mmol) was added slowly. The reaction mixture was then warmed to room temperature and stirred for 2 hours. Methanol (5.0 mL) was added slowly to the reaction followed by addition of saturated aqueous NH4Cl (100 mL). The reaction mixture was then extracted with EtOAc (2×300 mL), and the combined organic layers were washed with water (100 mL) and dried over anhydrous Na2SO4. Evaporation of solvent in vacuo followed by purification on a silica gel column (0 to 50% EtOAc/Hexanes) afforded trans-4-benzylhexahydrocyclopenta[b][1,4]oxazin-3(2H)-one. MS APCl calc'd for C14H17NO2 [M+H]+ 232. found 232.

1. temperatureThe reaction mixture was then warmed to room temperature
2. stirringstirred for 2 hours
3. extractionThe reaction mixture was then extracted with EtOAc (2×300 mL)
4. washthe combined organic layers were washed with water (100 mL)
5. dry with materialdried over anhydrous Na2SO4
6. customEvaporation of solvent in vacuo
7. customfollowed by purification on a silica gel column (0 to 50% EtOAc/Hexanes)

ORD record

ord-c56807adc6ec465588a06eb7c64df885

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846657B2