Ammonia → Lofexidine

HRID 463357Notes

Reaction equation

HRID 463357 reaction equation
C(O[C:4](=O)[CH:5]([O:7][C:8]1[C:13]([Cl:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15])[CH3:6])C.N.ClC1C=CC=C(Cl)C=1OC(C)C(N)=O.CN1CCOCC1.Cl.[NH2:40][CH2:41][CH2:42][NH2:43]>C(O)C.C(Cl)(Cl)Cl>[Cl:14][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:15])[C:8]=1[O:7][CH:5]([C:4]1[NH:40][CH2:41][CH2:42][N:43]=1)[CH3:6]

Participants

9

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 3301EthylenediamineHCID 79724-MethylmorpholineHCID 13177850Ethyl 2-(2,6-dichlorophenoxy)propanoateHCID 131778592-(2,6-Dichlorophenoxy)propanamide

Product 1

HCID 30668Lofexidine

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent3×HCID 6212ChloroformSolvent2×

Procedure

In a variation of the present process, the (-)-2-(2,6-dichlorophenoxy)-propionic acid ethylester obtained as above described, is reacted with an ethanolic solution of ammonia at room temperature and is converted into (+)-2-(2,6-dichlorophenoxy)-propionic acid amide which is difficultly soluble in ethanol. This amide is dehydrated at from 0° to 30° C. with a titanium tetrachloride/tetrahydrofurane complex and 4-methyl-morpholine in chloroform into (-)-2-(2,6-dichlorophenoxy)-propionic acid nitrile. By introducing hydrogen chloride at 0° C., the nitrile is then converted with ethanol in chloroform into (-)-2-(2,6-dichlorophenoxy)-propionimido acid ethylester hydrochloride. This compound is dissolved in ethanol and is cyclized by adding 1,2-diaminoethane to produce (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene. Analogously to the previous process, (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene hydrochloride is produced from the (-)-base thus obtained.

Sources & evidence

ORD record
ord-f2b5c06e54344ce2a3160672364e9fcb
Source dataset
uspto-grants-1985_05
Patent number
US04518783

Reaction notes

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