Ethanol → (4S)-4-cyclohexyl-L-proline

A solution of 2.0 g (0.0062 moles) of dehydro proline (prepared as described in Example 3) in 10 ml THF was added to a solution of lithium (0.65 g, 0.093 moles) in ammonia (150 ml) at ~-78° C. After the addition, the reaction mixture was stirred for 20 minutes and then absolute ethanol (3.6 ml, 0.062 moles) was added to the reaction mixture. The reaction mixture was stirred at -33° C. for 6 hours and quenched with 2.0 g of ammonium chloride. Ammonia was evaporated and the residue was acidified to pH=1 using 5% HCl and extracted with ethyl acetate (2×100 ml). Palladium hydroxide on carbon (20%, 0.25 g) was added to the aqueous layer and hydrogen gas was bubbled through the solution at room temperature for about 3 hours. It was filtered through a celite pad and the filtrate was concentrated and pH was adjusted to 6.3 by adding 5% NAOH solution. The precipitated product was filtered on the next day, and vacuum dried to obtain 0.52 g of trans-4-cyclohexyl-L-proline as white flaky solid.

1. additionAfter the addition
2. stirringThe reaction mixture was stirred at -33° C. for 6 hours
3. customquenched with 2.0 g of ammonium chloride
4. customAmmonia was evaporated
5. extractionextracted with ethyl acetate (2×100 ml)
6. additionPalladium hydroxide on carbon (20%, 0.25 g) was added to the aqueous layer and hydrogen gas
7. customwas bubbled through the solution at room temperature for about 3 hours
8. filtrationIt was filtered through a celite pad
9. concentrationthe filtrate was concentrated
10. additionby adding 5% NAOH solution
11. filtrationThe precipitated product was filtered on the next day, and vacuum
12. customdried

ORD record

ord-c44d5c7d685f4e05b434dff84237e684

Source dataset

uspto-grants-1988_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04734508