반응 #595305

반응 방정식

water

hydrochloric acid

3,6-bis[2-(methylthio)ethyl]-2,5-piperazinedione

( III )

3,6-bis[2-(methylthio)ethyl]-2,5-piperazinedione

→

methionyl-methionine

methionylmethionine

반응 조건

후처리

1. 1
   기타the apparatus was closed tightly
2. 2
   온도the mixture was cooled to 20° C.
3. 3
   세척The solid was washed with 10 l of water
4. 4
   세척The filtrate and washing water
5. 5
   기타were then collected in an 800 l container
6. 6
   workup.ADDITIONsubsequently introduced into a 500 l tank with stirrer again
7. 7
   workup.ADDITIONAddition of 2 kg of activated carbon
8. 8
   workup.STIRRINGby stirring at 20° C. for 30 min
9. 9
   여과The suspension was then filtered through a filter press into a further 500 l tank with stirrer
10. 10
    workup.ADDITIONAbout 28 l of concentrated ammonia solution were then added
11. 11
    기타to precipitate at pH 6 the DD/LL/DL/LD-methionylmethionine (I)
12. 12
    기타preferential precipitation of the less soluble racemic pair of diastereomers DL/LD-methionylmethionine (DL/LD-I)
13. 13
    농축the mother liquor was concentrated together with washing water to one quarter of the original volume in vapor pump vacuum at an internal temperature not
14. 14
    기타exceeding 40° C
15. 15
    기타During this, the more soluble racemic pair of diastereomers DD/LL-methionylmethionine (DD/LL-I) crystallized together with small amounts of the slightly soluble DL/LD-I
16. 16
    workup.DISTILLATIONCompletion of the distillation
17. 17
    온도by cooling to 20° C.
18. 18
    세척The separated mother liquor and washing water
19. 19
    기타Both fractions were dried in vacuo at 70° C

실험 절차

500 l of water were introduced into a 500 l enameled tank with stirrer, 32 l of concentrated hydrochloric acid and 78.6 kg of 3,6-bis[2-(methylthio)ethyl]-2,5-piperazinedione (III) (DKP) were added, and the apparatus was closed tightly. It was then heated at 110° C. while stirring for 2 hours, during which the pressure rose to 2.5 bar and the DKP (III) virtually completely dissolved. After the reaction was complete, the mixture was cooled to 20° C., and the unreacted DKP was spun down in a centrifuge. The solid was washed with 10 l of water. The filtrate and washing water were then collected in an 800 l container and subsequently introduced into a 500 l tank with stirrer again. Addition of 2 kg of activated carbon was followed by stirring at 20° C. for 30 min. The suspension was then filtered through a filter press into a further 500 l tank with stirrer. About 28 l of concentrated ammonia solution were then added to precipitate at pH 6 the DD/LL/DL/LD-methionylmethionine (I). During this there was an initial preferential precipitation of the less soluble racemic pair of diastereomers DL/LD-methionylmethionine (DL/LD-I). This was spun down and the mother liquor was concentrated together with washing water to one quarter of the original volume in vapor pump vacuum at an internal temperature not exceeding 40° C. During this, the more soluble racemic pair of diastereomers DD/LL-methionylmethionine (DD/LL-I) crystallized together with small amounts of the slightly soluble DL/LD-I. Completion of the distillation was followed by cooling to 20° C. and centrifugation. The separated mother liquor and washing water were discarded. Both fractions were dried in vacuo at 70° C. In total, it was possible to obtain 64.2 kg (78%) of DD/LL/DL/LD-methionyl-methionine (I) as mixture of diastereomers. Purity >98% (HPLC).

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