4-Methylmorpholine → HCID 56629305, compound

Temperature

-10 °C

11.57 g (50 mmoles) of tert.-butoxycarbonyl-D-norleucine and 5.6 ml (50 mmoles) of N-methylmorpholine are dissolved in 50 ml of dimethyl formamide. The solution is cooled to -10° C., and 6.6 ml (50 mmoles) of isobutyl chloroformate are added with stirring. After 10 minutes the mixture is cooled to -20° C., and a solution of 18.6 g (55 mmoles) of glycine benzyl ester p-toluolsulfonate and 6.1 ml (55 mmoles) of N-methylmorpholine in 80 ml of dimethyl formamide, cooled to -20° C., is added. The reaction mixture is stirred at -10° C. for 10 minutes, at 0° C. for one hour and then at room temperature overnight. The mixture is filtered, and the filtrate is evaporated under reduced pressure. The residue is dissolved in a mixture of 300 ml of ethyl acetate and 100 ml of water. The ethyl acetate phase is separated, washed successively with 5% aqueous sodium hydrocarbonate solution (2×60 ml), water (2×60 ml), 1 n hydrochloric acid cooled with ice water (2×60 ml) and water (2×60 ml) again, dried over sodium sulfate, decolourized with carbon, filtered, and the filtrate is evaporated under reduced pressure. The crystalline residue is triturated with diisopropyl ether, the solid is filtered off, washed with diisopropyl ether and dried. 14.65 g (76.9%) of tert.-butoxycarbonyl-D-norleucyl-glycine benzyl ester are obtained; m.p.: 85°-86° C., Rf13 =0.75-0.85, [α]D20 =+12.2° (c=1%, in dimethyl formamide).

1. temperatureAfter 10 minutes the mixture is cooled to -20° C.
2. additionis added
3. stirringThe reaction mixture is stirred at -10° C. for 10 minutes, at 0° C. for one hour
4. customat room temperature
5. customovernight
6. filtrationThe mixture is filtered
7. customthe filtrate is evaporated under reduced pressure
8. dissolutionThe residue is dissolved in a mixture of 300 ml of ethyl acetate and 100 ml of water
9. customThe ethyl acetate phase is separated
10. washwashed successively with 5% aqueous sodium hydrocarbonate solution (2×60 ml), water (2×60 ml), 1 n hydrochloric acid
11. temperaturecooled with ice water (2×60 ml) and water (2×60 ml) again
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. customthe filtrate is evaporated under reduced pressure
15. customThe crystalline residue is triturated with diisopropyl ether
16. filtrationthe solid is filtered off
17. washwashed with diisopropyl ether
18. customdried

ORD record

ord-f435f363baa140ac8b96e385d5440db9

Source dataset

uspto-grants-1982_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04339440