Citric Acid → Cbz-L-Phenylalaninal

Temperature

-60 °C

A solution of 24.5 ml of anhydrous dimethyl sulfoxide in 870 ml of anhydrous dichloromethane was cooled under N2 atmosphere to -60° C. and treated over a period of 15 min with 131 ml of a 2M solution of oxalyl chloride in dichloromethane in order that the internal temperature remained below -50° C. After addition, the solution was stirred at -60° C. for 15 min and treated over a period of 20 min with a solution of 50 g (0.175 mol) of Cbz-L-phenylalaninol in 200 ml of dichloromethane. The resulting solution was stirred at -60° C. for 1 h, then treated over a period of 15 min with 97 ml of triethylamine in order that the internal temperature remained below -50° C. After addition the solution was stirred at -60° C. for 15 min, then, with the cooling bath in place, was treated rapidly (over a period of 1 min) with a solution of 163 g of citric acid in 550 ml of water. The resulting slurry was stirred vigorously for 10 min, allowed to warm, diluted to 1 liter with water, and separated. The organic layer was washed with 700 ml of water followed by a mixture of 550 ml of water and 150 ml of saturated aqueous NaHCO3, dried over MgSO4, and concentrated in vacuo at 20° C. to give the crude desired compound as a light yellow solid.

1. customremained below -50° C
2. additionAfter addition
3. stirringThe resulting solution was stirred at -60° C. for 1 h
4. customremained below -50° C
5. additionAfter addition the solution
6. stirringwas stirred at -60° C. for 15 min
7. stirringThe resulting slurry was stirred vigorously for 10 min
8. temperatureto warm
9. customseparated
10. washThe organic layer was washed with 700 ml of water
11. additionfollowed by a mixture of 550 ml of water and 150 ml of saturated aqueous NaHCO3
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo at 20° C.

ORD record

ord-2c60202552974e2bba901d970fb6190f

Source dataset

uspto-grants-1996_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05541334