Ethanol → Lofexidine

HRID 325892Notes

Reaction equation

HRID 325892 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

50.2 g (=0.2646 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 30.0 g (=0.108 mols) of (+)-2-(2,6 -dichlorophenoxy)-propionic acid-N-(2-aminoethyl)-amide. A solution of 63.0 g (=0.5155 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), 16.0 g of (+)-2-[1-(2,6-dichlorophenoxy)ethyl]-1,3-diazacyclopent-2-ene C11H12Cl2N2O [259.1], are obtained, Mp: 127°-128° C.: [α]D20 =+80.6° (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), 16.0 g of (+)-2-[1-(2,6-dichlorophenoxy)ethyl]-1,3-diazacyclopent-2-ene C11H12Cl2N2O [259.1]
  5. customare obtained

Sources & evidence

ORD record
ord-a2df5556e16444638efd7be83555eb5f
Source dataset
uspto-grants-1984_04
Patent number
US04443464

Reaction notes

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