Patent GB-689234-A (GB)
Title: Improvements in and relating to the preparation of heterocyclic amino-alcohols and salts derived therefrom
Inventor: ADAMSON DONALD WALLACE
IPC: C07D213/38
Filed: 1948-07-20
Abstract: 3 - Tert. - amino - 1 - (21 - pyridyl) - 1 - aryl - propan-1-ols of the general formula <FORM:0689234/IV (b)/1> wherein R1 represents the 2-pyridyl radical, R2 represents an aryl radical or an alkoxy or halogen substituted aryl radical or the 2-thienyl radical, and R3 and R4 may be the same or different and represent alkyl radicals containing from 1 to 5 carbon atoms or NR3R4 denotes the morpholino, pyrollidino or piperidino radical, are prepared by treating the required tert.-aminoethyl aryl ketone, or a salt thereof, with 2-pyridyl-lithium, and hydrolysing the organo-lithium compound so formed.  The reaction may be carried out by forming a solution or suspension of 2-pyridyl-lithium in an inert solvent, e.g. ether, and mixing it with the aminoketone in an inert atmosphere while stirring. The organo-lithium compound formed may be hydrolysed with water followed by an acid, e.g. acetic or hydrochloric acid, and the acidic aqueous layer thus formed may then be separated, made alkaline and the basic product extracted with a solvent, e.g. chloroform.  The product may be purified by distillation under reduced pressure or by crystallization.  The product may be converted into a water-soluble salt.  In the examples the following compounds are prepared: 3-dimethylamino-1-(21-pyridyl)-1-phenylpropan-1-ol and its oxalate, 3 - N - pyrrolidino - 1 - phenyl - 1 - (21 - pyridyl) - propan-1-ol, 3-dimethylamino and 3-diethylamino-1-(41-chlorophenyl)-1-(211-pyridyl) propan - 1 - ol, 3 - N - pyrollidino - 1 - (41 - chlorophenyl) - 1 - (211 - pyridyl) propan - 1 - ol, 3 - dimethylamino - 1 - (41 - methoxyphenyl) - (21 - pyridyl propan-1-ol and its dihydrochloride, and 3 - dimethylamino - 1 - (21 - pyridyl) - 1 - (211 - thienyl) propan - 1 - ol.  The samples furnished under Sect. 2 (5) are 1-(41-bromophenyl) - 3 - N - morpholino - 1 - (211 - pyridyl) - propan - 1 - ol, and 1 - (41 - chlorophenyl) - 3 - N - piperidino - 1 - (211 - pyridyl) propan - 1 - ol.  Specifications 646,198, 689,288 and 689,289 are referred to.  3 - Dimethylamino - 1 - (31 - pyridyl) - phenylpropan - 1 - ol and 4 - N - piperidino - 1 - (21 - pyridyl)-2-phenylbutan-2-ol are referred to in the Provisional Specification and are prepared by a method similar to that given above.  2- and 3-Pyridyl-lithium are prepared by reacting lithium with 1-chlorobutane and adding 2-bromopyridine and 3-bromopyridine respectively.  b -Dimethylaminopropiophenone is prepared by reacting acetophenone, dimethylamine hydrochloride and formaldehyde.  b  - Dimethylamino - and b  - diethylamino - p - chloro-propiophenone are prepared by the reaction of p-chloroacetophenone, formaldehyde and dimethylamine and diethylamine respectively.  The hydrochloride salts of these compounds are mentioned.  b  - N - Pyrollidino - propiophenone is prepared by the reaction of acetophenone, formaldehyde and pyrollidine.  The hydrochloride salt is mentioned.  b  - N - Piperidino - propiophenone (referred to in the Provisional Specification) is prepared by the reaction of acetophenone, formaldehyde and piperidine.  b  - N - Pyrollidino- and b  - N - piperidino - p - chloro-propiophenone are prepared by reacting p - chloropropiophenone, formaldehyde and pyrollidine and piperidine respectively.  b  - N - Morpholino - p - bromo - propiophenone is prepared by reacting p-bromopropiophenone, formaldehyde and morpholine.