Chlorotrimethylsilane → N-(4-methoxybenzoyl)-L-valyl-L-proline

温度

0 °C

N-methylmorpholine (46 ml) was added to a mixture of L-valyl-L-proline hydrochloride (34 g) in THF (850 ml), followed by trimethylchlorosilane (41 ml) maintaining the temperature below 30° C. The mixture was stirred for 2 hours and then cooled to 0° C. Further N-methylmorpholine (16.5 ml) was added, followed by a solution of 4-anisoyl chloride (18 ml) in THF (25 ml), maintaining the temperature below 5° C. After 15 minutes, the mixture was filtered and the filtrate concentrated in vacuo to a yellow oil. The oil was dissolved in ethyl acetate (100 ml) and basified to pH 7-8 with saturated potassium bicarbonate solution (100 ml). The aqueous layer was separated and washed with ethyl acetate (50 ml). The aqueous layer was then acidified to pH 2-3 with 2M hydrochloric acid solution and extracted with ethyl acetate (150 ml). The organic extract was concentrated under vacuum and toluene (150 ml) was added. The solution was again concentrated under vacuum until about 50 ml of toluene was collected. The solution was then added dropwise to hexane (400 ml) with stirring to give a white solid, which was filtered, washed with hexane and dried under vacuum to give N-(4-methoxybenzoyl)-L-valyl-L-proline (40 g), having a similar NMR to that given in Procedure 1, step (iii) above.

1. temperaturemaintaining the temperature below 30° C
2. temperaturemaintaining the temperature below 5° C
3. waitAfter 15 minutes
4. filtrationthe mixture was filtered
5. concentrationthe filtrate concentrated in vacuo to a yellow oil
6. dissolutionThe oil was dissolved in ethyl acetate (100 ml)
7. customThe aqueous layer was separated
8. washwashed with ethyl acetate (50 ml)
9. extractionextracted with ethyl acetate (150 ml)
10. extractionThe organic extract
11. concentrationwas concentrated under vacuum and toluene (150 ml)
12. additionwas added
13. concentrationThe solution was again concentrated under vacuum until about 50 ml of toluene
14. customwas collected
15. additionThe solution was then added dropwise to hexane (400 ml)
16. stirringwith stirring
17. customto give a white solid, which
18. filtrationwas filtered
19. washwashed with hexane
20. customdried under vacuum

ORDレコード

ord-324d7a0198204ee0bcefbc68237c8172

出典データセット

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06037363