DE1199254B - Process for the preparation of O, N-dicarbaethoxy derivatives of substituted 1,3-amino alcohols - Google Patents

Description

GERMAN

PATENT OFFICE

EDITORIAL

German KL: 12 ο - 17/01

number
File number:
Registration date:
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K50881IVb / 12o
20th September 1963
August 26, 1965

The invention relates to a process for the preparation of O.N-dicarbethoxy derivatives of 2,2-disubstituted 1,3-amino alcohols of the general formula

R ₄

CH-O-COOC ₂ H ₅

Rs / I / R ₃

CH ₂ - NC

^X COOC ₂ H ₅

in which Ri and R _{2 are} identical or different and are alkyl, aralkyl or aryl radicals or a common »5 chain of four or five methylene groups, R3 is a hydrogen atom or an alkyl, aralkyl or aryl radical and R _{4 is} a hydrogen atom or a methyl group mean, where alkyl groups are understood to mean saturated or unsaturated, branched or unbranched aliphatic radicals of 1 to 6 carbon atoms.

The new compounds are prepared in a manner known per se from amino alcohols general formula

R ₄ -CH-OH

Ri \ l
c

Rs / 1 / R _{3 TO}

CH ₂ - NC '-

in which R 1 to R _{4 have} the meaning given above, by reaction with 2 moles of ethyl chloroformate in the presence of basic chlorine-hydrogen acceptors in an organic solvent or in a mixture of water and water-immiscible solvents, optionally with heating.

As amino alcohols subjected to this reaction are suitable, for example:

3-Amino-2.2-diethyI-propanol-1.
S-ethylamino ^ -ethyl ^ -benzyl-propanol-1,
S-methylamino ^ -ethyl ^ -benzyl-butanoI-1.
llihliZhl

Process for the production of
Ο, Ν-dicarbethoxy derivatives of substituted
1,3-amino alcohols

Applicant:

Krewel-Leuffen G. m. B. H., Eitorf / Sieg

Named as inventor:
Dipi.-Chem. Kurt Schmidt,
Zeil near Eßlingen / Neckar

The new compounds are substances that have a sedative effect on the central nervous system. For example, if one measures the sedative effect on the basis of the sleep prolongation test of hexobarbital sodium (hexobarbital = international abbreviation for cyclohexenyldimethylbarbituric acid) analogous to that of Holten and L arse η (Acta pharmacoL et toxicol., 12 [1956], p. 346 ff.) by applying 5% of the DL50 and determining the extension of the hexobarbital sleep after 2 hours, the result is that the compound described in the example (DL50: 3000 mg / kg) is almost 5 times as potent as the known one Ataractic Meprobamat (= international abbreviation for 2-methyl-2-n-propyl-propanediol dicarbamate) (DL50: 1230mg / kg) and 1.3 times as strong as the very similarly structured compound N- (2 , 2-diethyl - 3 - hydroxypropyl) - carbamic acid ethyl ester (DL ₅₀ : 1530 mg / kg) and prolongs sleep by 130%.

example

N- (propyl) -N- [2,2-diethyl-3-carbethoxyoxybutyl] -carbamic acid ethyl ester

jyy

propanol-1,
3-amino-2,2-pentamethylene-propanol-1,
3-anilino-2.2-diethyl-propanoI-l,
S-amino ^ -ethyl ^ -allylpropanol-1.
3-amino-2,2-diethylbutanol-1.
S-Benzylamino ^^ - diethylbutanol-1.

To a solution of 37.5 g of N-propyl-2,2-diethyl-3-hydroxypropylamine and 42 g. Triethylamine in 270 ml of absolute benzene is added dropwise while cooling with ice and stirring 44 g of ethyl chloroformate and then stirring for 2 hours at room temperature. Triethylamine hydrochloride is then filtered off with suction and the benzene phase is shaken with dilute Hydrochloric acid and then with bicarbonate solution, dried, concentrated and distilled in a high vacuum of 0.05 torr. At a boiling point one obtains

509 658/484

ΖΟ4

point from 109 to 111 ⁰ C 18 g product of the refractive index η ² D = 1.4542.

Claims (1)

Claim: Process for the preparation of O, N-dicarbethoxy derivatives of 1,3-amino alcohols of the general formula Ri \ CH-O-COOC ₂ H ₅ f I.
CH ₂ - / R ₃ COOC ₂ H ₅ 10 »5 in which Ri and R _{2 are} identical or different and are alkyl, aralkyl or aryl radicals or a common chain of four or five methylene groups, R _{3 is} a hydrogen atom or an alkyl, aralkyl or aryl radical, R * is a hydrogen atom or a methyl group and the alkyl radicals represent saturated or unsaturated, branched or unbranched aliphatic groups having 1 to 6 carbon atoms, characterized in that amino alcohols of the general formula are used in a manner known per se R ₄ CH-OH Ri \ l
c R ₂ Zf / R ₃ ch ₂ —n ( ^X H in the Ri to R4 the meaning given above have, with 2 Moi ethyl chloroformate in the presence of basic hydrogen chloride acceptors in an inert solvent or in a mixture of water and water-immiscible solvents, optionally under Warming up, converts. Considered publications:
Excerpted documents from Belgian patent No. 606 096. 5 »ί5 * ΛΜ8.65« Buadodnickcrei Bedm