Tropic acid → HCID 86744372, Verbindung

HRID 1110397

Reaktionsgleichung

Reaktionsgleichung von HRID 1110397
[OH:1][CH2:2][CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.C(Cl)(=O)OCC.[NH2:19][C:20]1[C:39]([Cl:40])=[CH:38][C:23]([C:24]([NH:26][C@H:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH2:35])[CH2:29][C@H:28]2[O:36][CH3:37])=[O:25])=[C:22]([O:41][CH3:42])[CH:21]=1>ClC(Cl)Cl.C(N(CC)CC)C>[NH2:19][C:20]1[C:39]([Cl:40])=[CH:38][C:23]([C:24]([NH:26][C@H:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH:35][C:4](=[O:6])[CH:3]([CH2:2][OH:1])[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:29][C@H:28]2[O:36][CH3:37])=[O:25])=[C:22]([O:41][CH3:42])[CH:21]=1

Komponenten

6

Edukt 3

HCID 10726Tropic acidHCID 10928Ethyl chloroformateHCID 14854954HCID 14854954, Verbindung

Produkt 1

HCID 86744372HCID 86744372, VerbindungAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a stirred suspension of 2.99 parts of α-(hydroxymethyl)benzeneacetic acid in 60 parts of trichloromethane were added dropwise first 1.82 parts of N,N-diethylethanamine and then 1.95 parts of ethyl carbonochloridate at a temperature below 5° C. Upon completion, stirring was continued for 45 minutes at this low temperature. The thus obtained solution was added dropwise to a solution of 5.35 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide in 45 parts of trichloromethane while the temperature was kept below 10° C. Upon completion, the whole was stirred for 20 hours at room temperature. The organic layer was washed with a sodium carbonate solution in water and with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile and a few drops of water. The product was filtered off and dried in vacuo at 30° C., yielding 0.76 parts (10.0%) of cis-N-[2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]ethyl]-α-(hydroxymethyl)benzeneacetamide; mp. 114.0° C. (compound 87).

Aufarbeitung

  1. customat a temperature below 5° C
  2. customwas kept below 10° C
  3. stirringUpon completion, the whole was stirred for 20 hours at room temperature
  4. washThe organic layer was washed with a sodium carbonate solution in water and with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile and a few drops of water
  13. filtrationThe product was filtered off
  14. customdried in vacuo at 30° C.

Quellen und Nachweise

ORD-Eintrag
ord-9f6afc79bc3f4c10a7e02cc5a4e440e5
Quelldatensatz
uspto-grants-1990_12
Patentnummer
US04975439

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