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

HRID 268230

Reaction equation

HRID 268230 reaction equation
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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Conditions

Temperature
0 °C

Procedure

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 5.9M 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).

Workup

  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 5.9M ethanolic hydrogen chloride
  10. customThe tacky precipitate was triturated with diethyl ether-acetone

Sources & evidence

ORD record
ord-5e10bcdf0fb24038a44267e7a1bba9a4
Source dataset
uspto-grants-1976_03
Patent number
US03947445

Linked notes

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