Hydrochloric Acid → 2-Chloro-5-(N,N-dimethylamino)ethyloxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

HRID 1532320Notes

Reaction equation

HRID 1532320 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:30][N:31]([CH3:35])[CH2:32][CH2:33]Cl.Cl>C(#N)C.C(OCC)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:33][CH2:32][N:31]([CH3:35])[CH3:30])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:11][CH:10]([CH2:16][CH:14]([CH2:13]3)[CH2:15]1)[CH2:9]2)=[O:5]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 227314932-Chloro-5-hydroxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 206700382-Chloro-5-(N,N-dimethylamino)ethyloxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamideYield 32.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-chloro-5-hydroxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamide from Example 51 (0.05 g) in acetonitrile (5 ml) was added potassium carbonate (0.065 g) and 2-dimethylaminoethyl chloride hydrochloride (0.037 g). The reaction mixture was stirred and heated at reflux temperature for 48 hours. The reaction mixture was evaporated under reduced pressure and residue dissolved in ethyl acetate and washed with brine. Drying over sodium sulphate (Na2SO4), followed by concentration under reduced pressure gave a residue which was subsequently purified by supercritical chromatography, eluting with CO2/methanol/0.1% diethylamine. Fractions containing product were concentrated under reduced pressure and the residue obtained was dissolved in diethyl ether. Hydrogen chloride (1 ml of a 1M solution in diethyl ether) was added dropwise and the resulting solid was triturated under diethyl ether and then dried in vacuo to leave the title compound as a white solid (0.020 g).

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 48 hours
  3. customThe reaction mixture was evaporated under reduced pressure and residue
  4. dissolutiondissolved in ethyl acetate
  5. washwashed with brine
  6. dry with materialDrying over sodium sulphate (Na2SO4)
  7. concentrationfollowed by concentration under reduced pressure
  8. customgave a residue which
  9. customwas subsequently purified by supercritical chromatography
  10. washeluting with CO2/methanol/0.1% diethylamine
  11. additionFractions containing product
  12. concentrationwere concentrated under reduced pressure
  13. customthe residue obtained
  14. customthe resulting solid was triturated under diethyl ether
  15. customdried in vacuo

Sources & evidence

ORD record
ord-7f98c776ecb347ef8929579437f1ea8c
Source dataset
uspto-grants-2001_03
Patent number
US06201024B1

Reaction notes

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