Chlorotrimethylsilane → 1-(4-Amino-5-chloro-2-methoxyphenyl)-5-(piperidin-1-yl)pentan-1-one hydrochloride

HRID 963377

Reaktionsgleichung

Reaktionsgleichung von HRID 963377
Cl.[N:2]1([CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:15][O:16][C:17]1[CH:26]=[C:25]([NH2:27])[C:24]([Cl:28])=[CH:23][C:18]=1C(OC)=O.Cl[Si](C)(C)C.N1(CCCCC(O)=O)CCCCC1>C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>[ClH:28].[NH2:27][C:25]1[C:24]([Cl:28])=[CH:23][C:18]([C:12](=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8][N:2]2[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[C:17]([O:16][CH3:15])[CH:26]=1

Komponenten

7

Edukt 4

HCID 6397ChlorotrimethylsilaneHCID 700493Methyl 4-amino-5-chloro-2-methoxybenzoate2×HCID 131720821-Piperidinepentanoic acidHCID 545927615-(Piperidin-1-yl)pentanoic acid hydrochloride

Produkt 1

HCID 97990091-(4-Amino-5-chloro-2-methoxyphenyl)-5-(piperidin-1-yl)pentan-1-one hydrochlorideAusbeute 160 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel4×HCID 2733832Lithium HexamethyldisilazideLösungsmittel3×

Versuchsvorschrift

A suspension of 5-(piperdin-1-yl)valeric acid hydrochloride (6.6 g, 30 mmol) in 100 mL of THF was cooled in an ice bath and 100 mL of 1N lithium bis(trimethylsilyl)amide in THF was added. The ice bath was removed and the resulting solution was stirred at room temperature for 1 hour. A mixture of methyl 2-methoxy-4-amino-5-chlorobenzoate (2.15 g, 10 mmol) and chlorotrimethylsilane (2.5 mL, 20 mmol) in 25 mL of THF was cooled in an ice bath and 20 mL of lN lithium bis(trimethylsilyl)amide in THF was addled. The solution containing the 5-piperdin-1-ylvaleric acid and iN lithium bis(trimethylsilyl)amide was cooled in an ice bath and the mixture containing the methyl 2-methoxy-4-amino-5-chlorobenzoate was added over 5 minutes. The reaction mixture was removed from the ice bath and stirred at 50°-55° C. for 2 hours and then a solution of 25 mL of concentrated hydrochloric acid in 175 mL of water was added. The mixture was stirred at 50°-55° C. under a gentle stream of nitrogen and then 120 mL of ethyl acetate was added. The mixture was stirred in an ice bath for 1 hour giving a precipitate. The precipitate was isolated by filtration and washed with ethyl acetate. The precipitate was stirred in approximately 40 mL of boiling isopropanol for 30 minutes and then for 1 hour in an ice bath. The precipitate was isolated by filtration and washed with isopropanol. Drying in a vacuum oven at between 55 and 60° C. under a nitrogen gas bleed for 18 hours gave 1-(4-amino-5-chloro-2-methoxyphenyl)-5-piperidin-1-ylpentan-1-one hydrochloride (2.9 g, 8 mmol).

Aufarbeitung

  1. temperaturewas cooled in an ice bath
  2. customThe ice bath was removed
  3. temperaturewas cooled in an ice bath
  4. additionwas added over 5 minutes
  5. customThe reaction mixture was removed from the ice bath
  6. stirringstirred at 50°-55° C. for 2 hours
  7. additiona solution of 25 mL of concentrated hydrochloric acid in 175 mL of water was added
  8. stirringThe mixture was stirred at 50°-55° C. under a gentle stream of nitrogen
  9. addition120 mL of ethyl acetate was added
  10. stirringThe mixture was stirred in an ice bath for 1 hour
  11. customgiving a precipitate
  12. customThe precipitate was isolated by filtration
  13. washwashed with ethyl acetate
  14. stirringThe precipitate was stirred in approximately 40 mL of boiling isopropanol for 30 minutes
  15. waitfor 1 hour in an ice bath
  16. customThe precipitate was isolated by filtration
  17. washwashed with isopropanol
  18. customDrying in a vacuum oven at between 55 and 60° C. under a nitrogen gas bleed for 18 hours

Quellen und Nachweise

ORD-Eintrag
ord-af9330aae52f4f41b16b54754aa4a608
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05763458

Verknüpfte Notizen

Wird geladen…