Hydrochloric Acid → HCID 6993082, compound

HRID 508123Notes

Reaction equation

HRID 508123 reaction equation
Cl.[CH3:2][S:3][CH2:4][CH2:5][CH:6]1[NH:11][C:10](=[O:12])[CH:9]([CH2:13][CH2:14][S:15][CH3:16])[NH:8][C:7]1=[O:17].[OH2:18]>>[NH2:8][C@H:9]([C:10]([NH:11][C@H:6]([C:7]([OH:17])=[O:18])[CH2:5][CH2:4][S:3][CH3:2])=[O:12])[CH2:13][CH2:14][S:15][CH3:16]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 1698423,6-bis[2-(methylthio)ethyl]piperazine-2,5-dione2×

Product 1

HCID 6993082HCID 6993082, compound

Conditions

Temperature
110 °C

Procedure

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).

Workup

  1. customthe apparatus was closed tightly
  2. temperaturethe mixture was cooled to 20° C.
  3. washThe solid was washed with 10 l of water
  4. washThe filtrate and washing water
  5. customwere then collected in an 800 l container
  6. additionsubsequently introduced into a 500 l tank with stirrer again
  7. additionAddition of 2 kg of activated carbon
  8. stirringby stirring at 20° C. for 30 min
  9. filtrationThe suspension was then filtered through a filter press into a further 500 l tank with stirrer
  10. additionAbout 28 l of concentrated ammonia solution were then added
  11. customto precipitate at pH 6 the DD/LL/DL/LD-methionylmethionine (I)
  12. custompreferential precipitation of the less soluble racemic pair of diastereomers DL/LD-methionylmethionine (DL/LD-I)
  13. concentrationthe 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. customexceeding 40° C
  15. customDuring 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. distillationCompletion of the distillation
  17. temperatureby cooling to 20° C.
  18. washThe separated mother liquor and washing water
  19. customBoth fractions were dried in vacuo at 70° C

Sources & evidence

ORD record
ord-a35522b2e4db434e837d2db69162b390
Source dataset
uspto-grants-2015_08
Patent number
US09095161B2

Reaction notes

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