MORPHOLINE AND PIPERAZINE DERIVATIVES

• Main Authors: MAISEY, ROY F, TURNER, RALPH W, MALLION, KEITH B
• Format: Patent
• Language: English
• Published: 10.12.1974
• Subjects: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; THEIR RELEVANT APPARATUS; TRANSPORTING

1310235 Heterocyclyloxymethyl - (morpholine or piperazine) derivatives IMPERIAL CHEMICAL INDUSTRIES Ltd 2 Nov 1970 [17 Nov 1969] 56087/69 Heading C2C [Also in Division A5] Novel compound I in which A is a heterocyclic fused ring other than a dioxide ring, which ring may be substituted, e.g. by OH, oxo, alkyl, aralkyl and alkoxycarbonyl; and X is O or NH and their acid addition salts are prepared by: (1) removal of the group or groups R from a compound II where R is α-aralkyl or alkyl and X1 is O or -NR-; e.g. by (a) hydrogenolysis or by (b) reaction with an alkyl or aryl chloroformate followed by hydrolysis; (2) cyclization of a compound III where Y is a displaceable radical; and (3) reaction of a compound IV with a compound H 2 NCH 2 CH 2 Y. 1 - (1,4 - Benzodioxan - 5 - yloxy) - 2,3 - epoxypropane is prepared by reacting ethanolic KOH with 1 - (1,4 - benzodioxanyloxy) - 3 - chloro- 2-propanol. 1 - (Benzo[b]furan - 7 - yloxy) - 2,3 - epoxypropane is prepared by a similar method to that given immediately above. 4 - Benzyl - 2(indol - 4 - yloxymethyl) - morpholine is prepared by reduction with LiAlH 4 of the corresponding morpholin-5-one, which is prepared by cyclization of 3-(N-benzyl-chloroacetamido) - 1 - (indol - 4 - yloxy) - 2 - propanol. The latter compound is prepared by reaction of chloroacetyl chloride with 3-benzylamino-1- (indol - 4 - yloxy) - 2 - propanol, prepared by reaction of benzylamine with 2,3-epoxy-1- (indol - 4 - yloxy) - propane. 2 - (Benzo[b]thien- 4 - yloxymethyl) - 4 - isopropyl - morpholine is prepared from 3-isopropylamino-1-(indol-4-yloxy)-2-propanol by a similar reaction sequence. 1,4 - Dibenzyl - 2 - (indol - 4 - yloxymethyl)- piperazine is prepared by reaction of 4-hydroxyindole with 1,4-dibenzyl-2-chloromethylpiperazine. Similarly prepared are 1,4-dibenzyl-2- (benzo[b]thien - 4 - yloxymethyl)piperazine diHCl; 1,4 - dibenzyl - 2 - (3 - methylbenzo[b]- thien - 5 - yloxymethyl)piperazine diHCl; and 1,4 - dibenzyl - 2 - (3 - methylbenzo[b]thien- 6- yloxymethyl)-piperazine diHCl. 4 - Benzyl - 2 - (1 - benzyl - 2 - methyl - indol- 5 - yloxymethyl) - morpholine is prepared by reaction of 4-benzyl-2-chloromethylmorpholine with 1 - benzyl - 5 - hydroxy - 2 - methyl - indole, prepared by decarboxylation of the corresponding 3-carboxyl derivative which is prepared by hydrolysis of the ethyl ester. 4 - Benzyl - 2 - (3 - ethoxycarbonyl - 2 - methylbenzo[b]furan - 5 - yloxymethyl)morpholine HCl, is prepared by reaction of ethyl 5-hydroxy-2- methylbenzo[b]furan - 3 - carboxylate with 4-benzyl-2-chloromethylmorpholine. 4 - Hydroxy - 3 - methyl - benzo[b]thiophen is prepared by decarboxylation of the corresponding 2-carboxyl derivative.