Reaction #1355082

Reaction equation

sodium borohydride

(1R*,3S*,5S*,6R*)-8-Benzyl-3-fluoro-1-phenyl-6-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octan-2-one

benzylamine

sodium hydroxide

→

title compound

Yield 31.7%

(1R*,2R*,3S*,5S*,6R*)-2-Benzylamino-8-benzyl-3-fluoro-1-phenyl-6-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octane

Yield 31.7%

Solvents

methanol

Conditions

Workup

1. 1
   Temperaturecooled
2. 2
   workup.ADDITIONAfter addition
3. 3
   Temperaturethe solution was heated for a further 16 hours
4. 4
   Temperaturecooled
5. 5
   OtherThe suspension formed
6. 6
   Extractionwas extracted with ethyl acetate (2×100 mL)
7. 7
   Dryingthe extracts were dried (MgSO4)
8. 8
   ConcentrationConcentration in vacuo
9. 9
   Othergave a gum which
10. 10
    Otherwas purified by silica chromatography

Procedure

(1R*,3S*,5S*,6R*)-8-Benzyl-3-fluoro-1-phenyl-6-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octan-2-one (Description 36a; 1.68 g, 4.1 mmol), titanium iso-propoxide (1.8 mL, 6.2 mmol) and benzylamine (520 μL, 4.7 mmol) were heated together at 85° C. for two hours, then cooled and diluted with methanol (30 mL). The solution was then heated to 50° C. and sodium borohydride (1.06 g, 28 mmol) was added portionwise over 4 hours. After addition was complete, the solution was heated for a further 16 hours, then cooled and poured into aqueous sodium hydroxide solution (100 mL, 1M). The suspension formed was extracted with ethyl acetate (2×100 mL) and the extracts were dried (MgSO4). Concentration in vacuo gave a gum which was purified by silica chromatography to give the title compound (651 mg, 1.3 mmol).

Source