Water → (1R,4S)-1-butyrylamino-4-(hydroxymethyl)-2-cyclopentene

温度

0 °C

34.7 g of (1R,4S)-1-amino-4-hydroxymethyl-2-cyclopentene hydrochloride and 2 g of 4-N,N-dimethylaminopyridine were dissolved in 600 ml of methylene chloride. The solution was cooled to 0° C. Then 52 g of triethylamine were added dropwise (5 min). The mixture was stirred for a further 30 min. A solution of 35.2 g of butyryl chloride in 60 ml of methylene chloride was metered into the mixture at 0C over the course of 1 h. The mixture was stirred for a further 1.5 h at between 0 and 20° C., and then 600 ml of water were added. After phase separation, the aqueous phase was extracted with 600 ml of methylene chloride. The combined organic phases were washed 3 times with 500 ml of 10% strength NaOH each time, and then completely evaporated. The dried solid was dissolved in 120 ml of methanol. The solution was mixed with 5 g of K2CO3 and stirred for a further 2 h at room temperature. The inorganic salts were filtered off and washed with 20 ml of methanol. The filtrate was neutralized with 2N HCl. The suspension was filtered and the filter cake was washed with 20 ml of methanol. The filtrate was completely evaporated. The solid residue was dried and crystallized in 150 ml of toluene. 28.5 g of title compound were obtained. The yield was 67%.

1. stirringThe mixture was stirred for a further 1.5 h at between 0 and 20° C.
2. customAfter phase separation
3. extractionthe aqueous phase was extracted with 600 ml of methylene chloride
4. washThe combined organic phases were washed 3 times with 500 ml of 10% strength NaOH each time
5. customcompletely evaporated
6. dissolutionThe dried solid was dissolved in 120 ml of methanol
7. additionThe solution was mixed with 5 g of K2CO3
8. stirringstirred for a further 2 h at room temperature
9. filtrationThe inorganic salts were filtered off
10. washwashed with 20 ml of methanol
11. filtrationThe suspension was filtered
12. washthe filter cake was washed with 20 ml of methanol
13. customThe filtrate was completely evaporated
14. customThe solid residue was dried
15. customcrystallized in 150 ml of toluene

ORDレコード

ord-5a0ae4274a8f43a79b2e4f0dcec24796

出典データセット

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06137007