Patent GB-795758-A (GB)
Title: Amino esters and the preparation thereof
IPC: C07D233/22
Filed: 1956-06-01
Abstract: The invention comprises compounds having the formula <FORM:0795758/IV (b)/1> wherein n is 2 or 3 and wherein at least one of the 1-, 4-, 5- and 6-positions within the alcohol residue is substituted by lower alkyl groups having from 1-6 carbon atoms, R is aryl containing non-functional substituents, R1 is hydrogen, hydroxy, lower alkyl or lower alkoxy, R11 is lower alkyl, cycloalkyl or aryl, acid addition salts thereof, and a process of preparing said compounds which comprises reacting a lower alkyl substituted 2-halomethyl-tetrahydropyrimidine or -dihydroimidazoline with an acid having the formula <FORM:0795758/IV (b)/2> wherein R, R1, and R11 are as hereinbefore defined. The halogen in the starting material may be chlorine, bromine or iodine.  The reaction is preferably effected in the presence of potassium iodide.  Alternatively the amino esters can be obtained by treating the corresponding amino ester minus its lower alkyl group within the alcohol residue, with a lower alkyl quaternizing agent, e.g. methyl bromide, ethyl chloride, propyl iodide, dimethyl sulphate and hexyl iodide.  The products are obtained as free esters or acid addition salts, e.g. hydrochloride, hydrobromide, hydriodide, acetate, nitrate, sulphate, lactate, citrate, phosphate and bitartrate.  Examples disclose the preparation of 4 - methyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl-a -cyclohexylphenylglycolate hydrochloride, 4 - methyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl - a  - cyclohexylphenylacetate hydrochloride, 4 - methyl - 1,4,5,6 - tetrahydro-2 - pyrimidylmethyl - a  - n - butylphenylglycolate hydrochloride, 4 - methyl - 4,5 - dihydro - 2 - imidazolylmethyl - a  - cyclohexylphenylglycolate hydrochloride, 1-methyl-1,4,5,6-tetrahydro-2-pyrimidylmethyl benzilate hydrochloride, 1-methyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclohexylphenylglycolate hydrobromide, 1 - methyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclohexylphenylglycolate hydrochloride, 1,4 - dimethyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclohexylphenylacetate hydrobromide, 1,4 - dimethyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclohexylphenylglycolate hydrobromide, 4-methyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclopentylphenylglycolate, 4 - methyl - 4,5 - dihydro - 2 - imidazolylmethyl a -cyclopentylphenylglycolate hydrochloride, 1-ethyl - 1,4,5,6 - tetrahydro - 2 - pyrimidyl - methyl a  - cyclohexylphenylglycolate hydrochloride, 1 - butyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclohexylphenylglycolate hydrochloride, 1 - ethyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclopentylphenylglycolate hydrochloride, 4-hexyl-4,5-dihydro-2-imidazolylmethyl a  - bistolylcaproate citrate, 1 - heptyl - 4,5 - dihydro - 2 - imidazolylmethyl a  - hydroxy - a  - bisnaphthylacetate lactate, 4 - propyl - 4,5 - dihydro - 2 - imidazolylmethyl bis-(parahydroxyphenyl)acetate phosphate, 6-pentyl - 1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - phenyl - a  - cycloheptylbutyrate bitartrate, 5 - propyl - 4,5 - dihydro - 2 - imidazolylmethyl a  - propoxy - a  - bisnaphthyl - acetate picrate, and 1-methyl-1,4,5,6 - tetrahydro - 2 - pyrimidylmethyl a  - cyclopentyl - a  - phenylglycolate hydrochloride.  Starting compounds.  2 - Chloromethyl - 4 - methyl - 1,4,5,6 - tetrahydro - pyrimidine hydrochloride is obtained from 1,3-diaminobutane and ethyl chlorimidoacetate hydrochloride.  The free base is obtained therefrom by treatment with caustic soda. b -Methylaminopropionitrile is obtained from acrylonitrile and methylamine.  This compound may be reduced with LiAlH4 and converted to N-methyl-1,3-diaminopropane hydrochloride.  2 - Hoydroxymethyl - 1 - methyl - 1 - methyl - 1,4,5,6 - tetrahydropyrimidine hydrochloride is obtained by treating N-methyl-1,3-diaminopropane with ethyl glycolimidate hydrochloride. The 2 - hydroxymethyl compound thus obtained is converted to the corresponding 2-chloromethyl compound by treatment with thionyl chloride.  a -Cyclopentylphenylglycolic acid is obtained in a Grignard reaction from cyclopentyl bromide and benzoyl formic acid. 2 - Hydroxymethyl - 4 - methylimidazoline hydrochloride is obtained by treating 1,2-diaminopropane with ethyl glycolimidate hydrochloride.  The 2-hydroxymethyl compound thus obtained is converted to the corresponding 2-chloromethyl compound by treatment with thionyl chloride.