Ethanol → Lofexidine

HRID 463359Notes

Reaction equation

HRID 463359 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C:5](=O)[CH:6]([O:8][C:9]1[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:16])[CH3:7].C(O)C>C(Cl)(Cl)Cl.O1CCCC1.CN(C)C1C=CN=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[Cl:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([Cl:15])[C:9]=1[O:8][CH:6]([C:5]1[NH:4][CH2:3][CH2:2][N:1]=1)[CH3:7]

Participants

7

Reactant 2

HCID 702EthanolHCID 13177851N-(2-Aminoethyl)-2-(2,6-dichlorophenoxy)propanamide

Product 1

HCID 30668Lofexidine

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 24193Titanium TetrachlorideCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

58.6 (0.3089 mols) of titanium tetrachloride are dissolved in a mixture of 700 ml of absolute chloroform and 25 ml of tetrahydrofuran at 0° C. and are mixed with 35.0 g (0.1263 mols) of (-)-2-(2,6-dichlorophenoxy)-propionic acid-N-(2-aminoethyl)-amide. A solution of 74.0 g (0.6056 mols) of 4-dimethylaminopyridine is then added dropwise very slowly at 0° C. with stirring and the mixture is further stirred for 36 hours at room temperature after the solution has been added. After working up and after purification by column chromatography (silica gel-dry column, eluant: chloroform/tetrahydrofuran 3:1), 21.0 g of (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene C11H12Cl2N2O [259.1], are obtained, Mp.: 126°-127° C.: [α]D20 =-80.2° (c=1/ethanol).

Workup

  1. stirringthe mixture is further stirred for 36 hours at room temperature after the solution
  2. additionhas been added
  3. customafter purification
  4. dry with materialby column chromatography (silica gel-dry column, eluant: chloroform/tetrahydrofuran 3:1), 21.0 g of (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene C11H12Cl2N2O [259.1]
  5. customare obtained

Sources & evidence

ORD record
ord-407d8cbc683f4a92b6a0418fc1b71273
Source dataset
uspto-grants-1985_05
Patent number
US04518783

Reaction notes

Loading…