Triethylamine → HCID 71354336, compound

Temperature

20 °C

To 13.9 ml (0.1 mol) of triethylamine in 100 ml of dry chloroform at 0° C. was added 9.1 g (0.05 mol) of D-Leu-OCH3.HCl. To this solution 4.5 ml (0.055 mol) of methanesulfonyl chloride was added at 0° C. while maintaining the reaction mixture above pH 8. After stirring at 20° C. for about 3 hours, the precipitated triethylamine hydrochloride was filtered and washed with chloroform. The filtrate was washed as follows: 1× with 50 ml 5% NaHCO3, 1× with 50 ml 10% KHSO4, 2× with 50 ml H2O. The organic layer was dried over anhydrous MgSO4, and the chloroform was evaporated under vacuum. The residual oil (Mes-D-Leu-OCH3, 10 g, 0.0446 mol) was dissolved at 10° C. in 50 ml of dry methanol containing 1.5 g of sodium. To this solution was added 3 ml of H2O and this reaction mixture was left for 72 hours at 20° C. The precipitate, Mes-D-Leu-ONa, was filtered, dried and dissolved in 50 ml of H2O. The solution was acidified to pH 2 with concentrated HCl. The solution was then extracted with chloroform, and the organic layer was dried over anhydrous MgSO4 and evaporated under vacuum. The residual oil (Mes-D-Leu-OH, 7.5 g, 0.0375 mol) was dissolved at 0° C. in 75 ml of chloroform containing 5.0 g (0.0375 mol) of Gly-OC2H5.HCl while maintaining the solution at pH 8 with triethylamine. To this solution at 0° C. was added 8.2 g (0.04 mol) of DCC in 15 ml of dry chloroform. This reaction mixture was held at 0° C. for 4 hours and then at 20° C. for 20 hours. The precipitated dicyclohexylurea was filtered and washed with CHCl3. The filtrate was washed with 30 ml 5% NaHCO3, 30 ml 10% KHSO4 and 2×30 ml of H2O, dried over anhydrous MgSO4 and evaporated under vacuum. The residual oil (Mes-D-Leu-Gly-OC2H5, 8.4 g, 0.03 mol) was dissolved in 45 ml of methanol, and to the solution was added 20 ml of 2N NaOH. The solution was held at 20° C. for 24 hours and then diluted with water to a volume of 100 ml. This solution was concentrated under vacuum to a volume of 35 ml; this mixture was washed with 15 ml of chloroform and neutralized with concentrated HCl to pH 3. The mixture was washed with 15 ml of chloroform and the water was evaporated under vacuum. The residue was dissolved in 50 ml of acetone, the precipitated NaCl was removed by filtration, and the acetone was evaporated under vacuum. Yield 47.4%; mp 122°-126° C.; [α]D20 =+4.0 (C 1; CH3OH); Anal. Calcd. for C9H18N2SO5 :C 40.59, H 6.81, N 10.52, S 12.04; Found:C 40.47, H 6.93, N 10.28, S 12.32.

1. temperaturewhile maintaining the reaction mixture above pH 8
2. filtrationthe precipitated triethylamine hydrochloride was filtered
3. washwashed with chloroform
4. washThe filtrate was washed
5. dry with materialThe organic layer was dried over anhydrous MgSO4
6. customthe chloroform was evaporated under vacuum
7. dissolutionThe residual oil (Mes-D-Leu-OCH3, 10 g, 0.0446 mol) was dissolved at 10° C. in 50 ml of dry methanol containing 1.5 g of sodium
8. additionTo this solution was added 3 ml of H2O
9. waitthis reaction mixture was left for 72 hours at 20° C
10. filtrationThe precipitate, Mes-D-Leu-ONa, was filtered
11. customdried
12. dissolutiondissolved in 50 ml of H2O
13. extractionThe solution was then extracted with chloroform
14. dry with materialthe organic layer was dried over anhydrous MgSO4
15. customevaporated under vacuum
16. waitThis reaction mixture was held at 0° C. for 4 hours
17. waitat 20° C. for 20 hours
18. filtrationThe precipitated dicyclohexylurea was filtered
19. washwashed with CHCl3
20. washThe filtrate was washed with 30 ml 5% NaHCO3, 30 ml 10% KHSO4 and 2×30 ml of H2O
21. dry with materialdried over anhydrous MgSO4
22. customevaporated under vacuum
23. dissolutionThe residual oil (Mes-D-Leu-Gly-OC2H5, 8.4 g, 0.03 mol) was dissolved in 45 ml of methanol
24. additionto the solution was added 20 ml of 2N NaOH
25. waitThe solution was held at 20° C. for 24 hours
26. additiondiluted with water to a volume of 100 ml
27. concentrationThis solution was concentrated under vacuum to a volume of 35 ml
28. washthis mixture was washed with 15 ml of chloroform and neutralized with concentrated HCl to pH 3
29. washThe mixture was washed with 15 ml of chloroform
30. customthe water was evaporated under vacuum
31. dissolutionThe residue was dissolved in 50 ml of acetone
32. customthe precipitated NaCl was removed by filtration
33. customthe acetone was evaporated under vacuum

ORD record

ord-7e8ec01a70114250abc1120339a341ce

Source dataset

uspto-grants-1995_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05399487