Acetone → (1S,3S)-1-(1,3-Benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic Acid Methyl Ester

HRID 2095094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2095094
[ClH:1].[CH3:2][O:3][C:4]([C@@H:6]1[CH2:18][C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C@H:8]([C:19]2[CH:27]=[CH:26][C:22]3[O:23][CH2:24][O:25][C:21]=3[CH:20]=2)[NH:7]1)=[O:5].[CH3:28][C:29](C)=[O:30]>ClCCl.C(=O)(O)[O-].[Na+]>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:18][C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C@H:8]([C:19]2[CH:27]=[CH:26][C:22]3[O:23][CH2:24][O:25][C:21]=3[CH:20]=2)[N:7]1[C:29](=[O:30])[CH2:28][Cl:1])=[O:5]

Komponenten

5

Edukt 2

HCID 180AcetoneHCID 44250481Tadalafil Impurity 11

Produkt 1

HCID 68502869(1S,3S)-1-(1,3-Benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic Acid Methyl Ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Cis 1 -Benzo[1,3]dioxol-5 -yl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester hydrochloride (50 g) was dissolved in dichloromethane and 5% aqueous sodium bicarbonate (500 mL). The organic layer was separated and washed with deionized water (500 mL). The organic layer was added into deionized water (50 mL) and treated with sodium bicarbonate (15 g) at 25-30° C. To the resultant mixture chloroacetyl chloride (25 g) in dichloromethane (50 mL) was added at a rate sufficient to maintain the temperature of the reaction mixture between 0 and 5° C. The reaction mixture was stirred for three hours. After the completion of reaction, dichloromethane (500 mL) and DI water (1 L) were added. The organic layer was separated and washed sequentially with water followed by aqueous sodium bicarbonate solution till pH was 6.5-7.0, and finally with water. The organic layer was concentrated under reduced pressure to obtain a solid. The solid was dissolved in acetone (750 mL) and the resultant solution was concentrated to a residual volume of about 75 mL. To the concentrated solution, deionized water was slowly added at 20-25° C. and the resultant mixture cooled to 0-5° C. with continuous stirring for 0.5 hours. The solid so obtained was filtered and dried to afford cis 1-benzo[1,3]dioxol-5-yl-2-(2-chloro-acetyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester.

Aufarbeitung

  1. customThe organic layer was separated
  2. washwashed with deionized water (500 mL)
  3. additionThe organic layer was added into deionized water (50 mL)
  4. additiontreated with sodium bicarbonate (15 g) at 25-30° C
  5. additionTo the resultant mixture chloroacetyl chloride (25 g) in dichloromethane (50 mL) was added at a rate sufficient
  6. temperatureto maintain the temperature of the reaction mixture between 0 and 5° C
  7. customAfter the completion of reaction, dichloromethane (500 mL) and DI water (1 L)
  8. additionwere added
  9. customThe organic layer was separated
  10. washwashed sequentially with water
  11. concentrationThe organic layer was concentrated under reduced pressure
  12. customto obtain a solid
  13. concentrationthe resultant solution was concentrated to a residual volume of about 75 mL
  14. additionwas slowly added at 20-25° C.
  15. stirringwith continuous stirring for 0.5 hours
  16. customThe solid so obtained
  17. filtrationwas filtered
  18. customdried

Quellen und Nachweise

ORD-Eintrag
ord-c492df44721745cf93e250e4b808b4e2
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08445698B2

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