Diethylcarbamoyl chloride → 2-benzyl-5-(N,N-diethyl-carbamyl)2,5-diazabicyclo[2.2.1]heptane hydrochloride

HRID 1605953

Reaktionsgleichung

Reaktionsgleichung von HRID 1605953
S(N1CCC[C@@]1(O)CO)(C1C=CC(C)=CC=1)(=O)=O.S([N:29]1[CH2:34][CH:33]2[CH2:35][CH:30]1[CH2:31][N:32]2[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)(C1C=CC(C)=CC=1)(=O)=O.I.I.C(N1CC2CC1CN2)C1C=CC=CC=1.CC(C)=NNC(C1C=C([Cl:71])N=C(Cl)C=1)=O.[OH-].[Na+].[CH2:76]([N:78]([CH2:82][CH3:83])[C:79](Cl)=[O:80])[CH3:77]>C(Cl)(Cl)Cl.O>[ClH:71].[CH2:36]([N:32]1[CH2:31][CH:30]2[CH2:35][CH:33]1[CH2:34][N:29]2[C:79](=[O:80])[N:78]([CH2:82][CH3:83])[CH2:76][CH3:77])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Komponenten

9

Edukt 6

HCID 6916Diethylcarbamoyl chlorideHCID 14798Sodium HydroxideHCID 27511Isonicotinic acid, 2,6-dichloro-, isopropylidenehydrazideHCID 2914126-Benzyl-3-(4-methylphenyl)sulfonyl-3,6-diazabicyclo[2.2.1]heptaneHCID 224039562-Benzyl-2,5-diazabicyclo[2.2.1]heptane dihydroiodide2×HCID 67796897N-Tosylhydroxy-L-prolinol

Produkt 1

HCID 215454962-benzyl-5-(N,N-diethyl-carbamyl)2,5-diazabicyclo[2.2.1]heptane hydrochlorideAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

N-Tosylhydroxy-L-prolinol was converted to 2-tosyl-5-benzyl-2,5-diazabicyclo[2.2.1]heptane which in turn was cyclized to N-benzyl-2,5-diazabicyclo[2.2.1]heptane dihydriodide all according to the procedures reported by P. S. Portoghese and A. A. Mikhail in J. Org. Chem., 31, p 1059, 1966. A two-phase mixture of 6.0 g (0.0135 mole) 2-benzyl-2,5-diazabicyclo[2.2.1]heptane dihydroiodide, 27 ml 20% aqueous sodium hydroxide, and 50 ml chloroform was stirred 1 hour at 0° C. Diethylcarbamyl chloride (2.75 g, 0.0202 mole) in 5 ml chloroform was added and the mixture stirred at 0° C for 1 hour. After 68 hours at ambient temperature, 50 ml hot water was added, and 30 minutes later the organic phase was isolated. One chloroform extract of the aqueous phase was combined with the original organic phase, and the solution was dried with sodium sulfate. Evaporation to dryness in vacuo left 4.87 g of oily crude product that was chromatographed on alumina with chloroform elution. The purified product in 100 ml diethyl ether was converted to the salt by addition of dry 5.9 M ethanolic hydrogen chloride. The tacky precipitate was triturated with diethyl ether-acetone to give pure 2-benzyl-5-(N,N-diethyl-carbamyl)2,5-diazabicyclo[2.2.1]heptane hydrochloride (3.2 g, 80% yield, melting point 147°-149° C).

Aufarbeitung

  1. stirringthe mixture stirred at 0° C for 1 hour
  2. waitAfter 68 hours at ambient temperature
  3. custom30 minutes later the organic phase was isolated
  4. extractionOne chloroform extract of the aqueous phase
  5. dry with materialthe solution was dried with sodium sulfate
  6. customEvaporation to dryness in vacuo
  7. waitleft 4.87 g of oily crude product that
  8. customwas chromatographed on alumina with chloroform elution
  9. additionThe purified product in 100 ml diethyl ether was converted to the salt by addition of dry 5.9 M ethanolic hydrogen chloride
  10. customThe tacky precipitate was triturated with diethyl ether-acetone

Quellen und Nachweise

ORD-Eintrag
ord-aafa01447a5f45428781af96e279f461
Quelldatensatz
uspto-grants-1976_04
Patentnummer
US03951980

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