Patent GB-765874-A (GB)
Title: Improvements in or relating to methods of preparing chemical compounds containing the pyrrocoline nucleus and new chemical compounds produced thereby
Inventor: BARRETT PAUL ANTHONY
IPC: C07D471/04
Filed: 1953-12-21
Abstract: A method of preparing compounds containing the pyrrocoline nucleus comprises reacting a 1-(2 - pyridyl) - 3 - tertiary aminopropan - 1 - ol or a 1 - (2 - pyridyl) 3 - tertiary aminoprop - 1 - ene with acetic anhydride and separating the resulting pyrrocoline from the reaction mixture.  The process is applicable to the reaction with acetic anhydride of compounds of the formula: <FORM:0765874/IV(b)/1> and <FORM:0765874/IV(b)/2> respectively, in which R1 is a phenyl or 2-thienyl group (either of which may carry as substituents chloro, bromo, alkyl or alkoxy groups), a 2-pyridyl or an alkyl group; R2 is hydrogen or a methyl or phenyl group; or R1 and R2 form a fully reduced cyclic structure having 5, 6, or 7 carbon atoms; R3 is hydrogen, or when R4 is hydrogen, is a methyl or phenyl group; R4 is hydrogen or methyl, except that when R1 is 2-pyridyl, R4 is hydrogen; NR5R6 is a tertiary amino group in which R5 and R6 may either be alkyl groups or together form a cyclic structure; R7 is phenyl or thienyl, which may carry substituents as listed for R1, the product being a pyrrocoline of the general formula: <FORM:0765874/IV(b)/3> in which R8 is an acetyl group or, when R3 is methyl or phenyl, R8 is methyl or phenyl.  Reference is also made to the use of propionic anhydride.  In examples: (1) 1-p-chlorophenyl - 1 - (2-pyridyl) - 3 - pyrrolidinopropan - 1 - ol is boiled with acetic anhydride to give 3-acetyl-1-p - chlorophenylpyrrocoline; (2) 1 - p - chlorophenyl - 1 - (2 - pyridyl) - 3 - pyrrolidinoprop - 1 -ene refluxed with acetic anhydride, acetic acid and sodium acetate gives the same product as in (1); (3) and (4) 3-acetyl-1-phenylpyrrocoline is prepared similarly from 1 - phenyl - 1 - (2-pyridyl) - 3 - pyrrolidinopropan - 1 - ol and 1 phenyl - 1 - (2 - pyridyl) - 3 - pyrrolidinoprop - 1-ene respectively.  In further examples there are similarly prepared (from starting materials which include the carbinols described below or the corresponding allylamines) (5) and (6) 3 - acetyl - 2 - methyl - 1 - phenylpyrrocoline; (7) and (8) 3 - acetyl - 1 - p - chlorophenyl - 2-methyl - pyrrocoline; (9) and (10) 3 - acetyl-1 : 2 - diphenylpyrrocoline (11) 3 - acetyl - 1 - p - chlorophenyl - 2 - phenylpyrrocoline; (12) and (13) 1 - phenyl - 3 - methylpyrrocoline; (14) 1 - p - chlorophenyl - 3 - methylpyrrocoline; (15) and (16) 1 : 3 - diphenylpyrrocoline; (17) 3 - acetyl - 1 - p - anisylpyrrocoline; (18) 3-acetyl - 1 - o - tolylpyrrocoline; (19) 3 - acetyl-8 - methyl - 1 - phenylpyrrocoline; (20) 3-acetyl - 8 - methyl - 1 - p - chlorophenylpyrrocoline; (21) 3 - acetyl - 1 - (5 - chlorothienyl-2) pyrrocoline; (22) 3 - acetyl - 1 - (2 - pyridyl) pyrrocoline; (23) 3 - acetyl - 1 - methylpyrrocoline; (24) 3 - acetyl - 1 - ter - butylpyrrocoline; (25) 6 - acetyl - cyclohexa (9) - pyrrocoline for which the starting material, 2-dimethylaminomethyl - 1 - (2 - pyridyl) - cyclohexan - 1 - ol is prepared by the reaction of 2 - dimethylaminomethylcyclohexan - 1 - one with pyridyllithium.  New carbinols, prepared for use as starting materials by the method of Specification 689,234, are 1-phenyl-1-(2-pyridyl)-3-piperidinoisobutan - 1 - ol 1 - p - chlorophenyl - 1 - (2-pyridyl) - 3 - piperidinoisobutan - 1 - ol, 1 : 2-diphenyl - 1 - (2 - pyridyl) - 3 - piperidinopropan-1 - ol, 1 - p - chlorophenyl - 2 - phenyl - 1 - (2-pyridyl) - 3 - pyrrolidinopropan - 1 - ol, 1-phenyl - 1 - (2 - pyridyl) - 3 - piperidinobutan-1 - ol, 1 - p - chlorophenyl - 1 - (2 - pyridyl) - 3 - pyrrolidinobutan - 1 - ol, 1 : 3 - diphenyl - 1 - (2-pyridyl) - 3 - piperidinopropan - 1 - ol 1 - phenyl - 1 - (3 - picolyl - 2) - 3 - pyrrolidinopropan- 1-ol, 1 - p - chlorophenyl - 1 - (3 - picolyl - 2) - 3-pyrrolidinopropan - 1 - ol, 1 - o - tolyl - 1 - (2-pyridyl) - 3 - piperidinopropan - 1 - ol, 2 - (2-pyridyl) - 4 - piperidinobutan - 2 - ol, 3 - (2-pyridyl) - 2 : 2 - dimethyl - 5 - piperidinopentan-3 - ol, and 1 : 1 - di - (2 - pyridyl) - 3 - dimethylaminopropan-1-ol.  As intermediates for such carbinols are prepared 1-phenyl-3-piperidinobutan - 1 - one (by reacting piperidine with crotonophenone), 1 - p - chlorophenyl - 3 - pyrrolidinobutan - 1 - one (by reacting pyrrolidine with p - chlorocrotonophenone), 1 : 3 - diphenyl - 3 - piperidinopropan - 1 - one (by reacting benzalacetophenone with piperidine), and 1 - phenyl - 3 - piperidinoisobutan - 1 - one, 1-p - chlorophenyl - 3 - piperidinoisobutan - 1-one, 1 : 2 - diphenyl - 3 - piperidinopropan - 1-one, 1 - p - chlorophenyl - 2 - phenyl - 3 - pyrrolidinopropan - 1 - one, 4 - piperidinobutan - 1-one and 5 - piperidino - 2 : 2 - dimethylpentan-3-one (by the Mannich reaction).  Specifications 701,445 and 719,276 also are referred to.