4-Methylmorpholine → HCID 56639216, compound

To a vigorously stirred solution of [(t-butyloxy)carbonyl]-L-alanine (15.14 g, 80 mmol) and N-methylmorpholine (8.80 ml, 80 mmol) in 80 ml of dry tetrahydrofuran at -15° C. under argon was added a solution of isobutyl chloroformate (10.37 ml, 80 mmol) in 10 ml tetrahydrofuran, maintaining the reaction temperature below -12° C. After the addition was complete, the reaction mixture was stirred for 14 minutes and then diluted with 250 ml of anhydrous ether (prechilled to -20° C.) and quickly filtered. Approximately one-fourth of the filtrate was transferred to a separatory funnel (the remainder kept chilled) and added rapidly to a gently stirred, chilled (0° C.) solution of diazomethane (160 mmol, generated from 23.54 g of N-methyl-N'-nitro-N-nitrosoguanidine). Additional chilled portions were transferred to the separatory funnel until the entire solution had been added (over approximately 10 minutes). The resulting solution was stirred for 2 hours, warming gradually to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml), dried (sodium sulfate) and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C., plus an additional crop of 1.33 g, melting point 97.5°-101° C. A portion was recrystallized once more giving the analytical sample, melting point 102°-103° C.

1. temperaturemaintaining the reaction temperature below -12° C
2. additionAfter the addition
3. filtrationquickly filtered
4. customApproximately one-fourth of the filtrate was transferred to a separatory funnel
5. temperature(the remainder kept chilled) and
6. additionadded rapidly to
7. stirringa gently stirred
8. temperatureAdditional chilled portions
9. additionhad been added (over approximately 10 minutes)
10. stirringThe resulting solution was stirred for 2 hours
11. custompurged with nitrogen for 1 hour
12. washwashed with chilled half-saturated sodium bicarbonate (2×100 ml) and water (3×50 ml)
13. dry with materialdried (sodium sulfate)
14. customevaporated to a yellow semi-crystalline residue
15. customTwo recrystallizations from ethyl acetate-petroleum ether yielded yellow plates, 10.29 g, melting point 99°-102° C.
16. customA portion was recrystallized once more
17. customgiving the analytical sample, melting point 102°-103° C.

ORD record

ord-7fc4adc8e13544c2b8bbeaae78fe8920

Source dataset

uspto-grants-1986_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04594188