SU1294808A1 - Method for producing 1-triethylsiloxy-2(n,n-methylalkylamino)ethanes - Google Patents

Abstract

The invention relates to organosilicon compounds, in particular, a method for producing 1-triethylsiloxy 2 (H, M-methalkylamino) ethanes (SET), which are used in medicine as biologically active substances. To increase the yield of ETS, another hydroxylamine derivative, 3-apkyl-1,3-oxazacyclopentane, is used, another catalyst, reduced nickel, and other reaction temperature conditions — 128-132 ° C fi temperature to the closed system (ampoule or pressurized reactor). The method allows to avoid the loss of triztilsilan, which evaporates when heated, and the absence; the release of hydrogen makes the process explosion-proof. The yield of CET increased to 95, -3%. y co 4; 00

Description

one

This invention relates to organic chemistry, specifically to a process for the preparation of 1-triethylsiloxy -.- (N, N-methyl alkyl amino) ethanyl formula

/ R

; s, n ,;

SiOCH CH H

sn.

where R -.,., cyclo-C H, which are biologically active substances and precursors of (M, N-dialkylamino) ethanols.

The aim of the invention is to increase the yield of the target product.

Example 1, Preparation of reduced nickel,

1.3 g (s501 mol) of nickel chloride are calcined in a porcelain crucible at 200–250 ° C for 20 minutes, then noMeutafoT into a heated 5 ml tube with section 5 is filled with 2.32 ml (0.02 mol) of triethylsilane i; heated under reflux in an oil bath at 130–150 ° C for 20 min. In this case, the reaction mixture acquires a black color, which indicates the recovery of nickel. Then the tube is removed, allowed to cool to a temperature of 50-60 ° C, and the triethylchlorosilane formed is carefully poured out. At the same time, heavy nickel particles remain at the bottom of the tube. The tube is again attached to the cooler 5 and placed in a bath (130-150 ° C), the calculated amount of triethylsilane used in the reaction is poured through the cooler, and agitated for another 10 minutes. After that, the mixture is cooled in a drying tube to 50-60 ° C, shaken well and used in reaction with 1,3-oxazacyclopentane, I

This method of nickel reduction is optimal because it uses triethsilane, which is one of the reagents

P and Measure 2, B glass bottle) vial or sealed reactor sarpyKaJOT 8.7 g (0.1 mol), 3-methyl-I, 3-oxa, cyclopentane,. 1 1, 6 g (o, mol) tr of ethylsilane and 0.59 g (0.0 mol) of reduced nickel. The vial is sealed or the reactor is sealed and kept in a thermostat at 130 ° C for 3 hours. After storp, by vacuum distillation 19.3 g | triet; 1Lsiloxy-2-drmethylaminoethane. Yield 95%, t, bale, 86.0 ° С, dlq 0.8470, 62.84, MRB

 D

- 1.4350, MRi

rpsc

O

five

Example 3. Analogue Example 1, the reagents were loaded, but the reaction was carried out without sealing, in a flask with a reflux condenser, in an oil bath heated to 130 ° C. 6.2 g of 1-triethylsiloxy-2-dimethylaminoethane are recovered (80%).

As can be seen from examples i and 2, the presence of air in the system does not hinder the progress of the reaction, but in a closed system the product yield is higher, i.e. an increase in pressure favors the reaction, and the reaction in the ampoule also avoids the loss of triethylsilane, which partially evaporates during prolonged heating, despite the reflux condenser. Carrying out the reaction in the ampoule furthermore simplifies installation and, therefore, is optimal. At the same time, no hydrogen is generated during the reaction, which makes the installation fire and explosion safe.

Further optimization of the reaction conditions is carried out using Z-butyl-1,3-oxazacyclopenane as the hydrosilation object.

Example 4. 14.3 g (0.1 mol) of 3-butyl-1,3-oxazacyclopentane, 11.6 g (0.1 mol) of triethylsil. Ana and 0.59 are charged into a glass amnoule or a sealed reactor. g (0.01 mol) of reduced nickel. Sealed ampoule or sealed

0

five

0

five

0

five

0

five

The reactor was kept in a thermostat at 130 ° C for 3 hours. After this, 23.3 g of 1-triethylsiloxy-2 (M, N-methylbutyl amino) ethane was isolated by vacuum distillation. 95% yield, b.p. 132 C / / 10 ml of mercury. D 0.8370,

P

20

eleven

Mrp

ml of mercury, Art. ,

- 1.4375, MRDpc, c4. 76.9 i .CC ,, 6,64,

EXAMPLE 5 Analogously to Example 3, 11.6 g (0.1 mol) of triethylsilane and 0.59 g (OjO mol) of reduced are added to 14.3 g (0.1 mol) of 3-butyl-153-oxazacyclonentane. nickel The synthesis is carried out at 120 ° C for 3 hours. After vacuum distillation, 4.95 g of | -tr ethylsilox-2- (M, N-methylbutylamino) ethane is obtained. Yield 61%.

Example 6 Analogously to Example 3, P, 6 g (0.1 mol) of triethylamine and 0.59 g (0.01 mol) of the reduced are added to 14.3 g (0.1 mol) of 3-butyl, 3-oxazacyclopentane. nickel Synthesis is carried out at 125 ° C.

after 3 hours. After vacuum distillation, 19.8 g of α-triethyl siloxane72- (N, N-methylbutylamino) ethane is obtained. The yield is 80.6%.

Example 7. Similarly to Example 3, 11.6 g (.0.1 mol) of triethylsilane and 0.59 g are added to 14.3 g (0.1 mol) of 3-butyp-1,3-oxazacyclopentane.

(0.0 mol) reduced nickel

about

The synthesis is carried out at 40 ° C for 3 hours. After vacuum distillation, 18.2 g of 1-triethylsiloxy-2- (M, M methylbutylamino) ethane are obtained. Yield 74%.

Example 8. Analogously to Example 3, 11.6 g (0.1 mol) of triethylsilane and 0.59 g (0.01 mol) were added to 14.3 g (0.1 mol) of 3-butyl-i, 3-oxazocyclopentane reduced nickel. The synthesis was carried out at 135 ° C for 3 hours. After vacuum distillation, 20.13 g of 1-triztilsiloxy-2- (M, N-methylbutylamino) ethane was obtained. Yield 82.1%.

Example 9. In a similar manner to Example 3, the synthesis was carried out at 128 ° C. 22.3 g of 1-triethylsiloxy-2- (N, N-methylIbutylamino) ethane are obtained. Yield 90.8%.

Example 10. Analogously to Example 3, the synthesis was carried out at 132 ° C. 22.1 g of 1-triethylsiloxy-2- (N, M-methylbutyamino) ethane are obtained. Yield 90.0%.

On the basis of examples 1-7, it can be seen that the optimum temperature for this reaction is 128

132 C. In this range, the product yield is 90-95%. With a temperature of 10 ° C, the yield is reduced by 21%. When the temperature drops by 10 ° C, the yield decreases by 34%.

Example 11. Analogously to Example 3, 12.76 g (0.11 mol) of triethylsilane and 0.59 g (0.1 mol) were added to 14.3 g (0.1 mol) of 3-butyl-1,3-oxazadiclopentane. reduced nickel. The synthesis is carried out at 130 ° C for 3 hours. After vacuum distillation, 23.2 g of 1-triethylsiloxy-2- (N, N-methylbutylamino) ethane are obtained. Exit 94.5%.,

Example 12. Analogously to Example 3, 11.6 g (0.1 mol) of triethylsilane and 0.59 g (0.1 mol) were added to 15.73 g (0.11 mol) of 3-butyl-1,3-oxazacyclopentane. reduced nickel. The synthesis is carried out for 3 hours. After vacuum distillation, 20.9 g of 1-triethylsil are obtained.

,

at

,

15

20

25

thirty

35

948084

Si-2- (N, N-methylbutylamino) ethane. Yield 85%.

From Examples 8 and 9 it can be seen that Excess, triethylsilane does not affect the product yield. However, carrying out the reaction in excess of triethylsilane is uneconomical. When the reaction is carried out in excess of 3-butyl-1,3-oxazacyclopentane, the yield of the product decreases due to the complexity of its isolation by vacuum distillation. Thus, the opt. the most is a 1: 1 molar ratio of reactants.

P-f and mep 13. Similarly, an example of a gum size of 14.3 g (0.1 mol) of 3-butyl-. 1,3-oxazacyclopentane 11.6 g (0.1 mol) of triethylsilane and 0.88 g (0.15 mol) are added

fO

40

reduced nickel. The synthesis is carried out at 130 ° C for 3 hours. After vacuum distillation, 23.4 g of 1-triethylsiloxy-2- (N, N-methyl butyl amino) ethane are obtained. Yield 95.3%.

Example 14. Analogously to Example 3, 11.6 g (0.1 mol) of triethylsilane and 0.41 g (0.007 mol) of reduced nickel were added to 14.3 g (0.1 mol) of 3-butyl-I, 3-oxazacyclopentane. . The synthesis is carried out at 130 ° C for 3 hours. After vacuum distillation, 12.6 g of 1-triethylsiloxy-2- (N, N-methyl butyl amine o) ethane a are obtained. Yield 51, 3%.

Example 15. 15.6 g (0.1 mol) of 3-cyclohexyl-1,3-oxazacyclopentane, 15.6 g (0.1 mol) were charged to a glass ampoule or a resealable reactor. 11.6 g (0.1 mol) of triethylsilane and 0.59 g (0.01 mol) of reduced nickel. Seal the vial or seal the terch.

Thereafter, 25.8 g of 1-triethylsiloxy-2- (N, l-methylcyclohexyl) was distilled by vacuum distillation. Tty a 95% run, b.p. (6 mm Hg)

. 9O. 70 , -.

stand the reactor and incubate at 130 C for 3

20

MR

 0.8892, p

1, 4619,

DpacM 83.94, MRD., Kcn "3.72. Example 16, In glass. A vial or a pressurized reactor was charged with 11.5 g (0, .1 mol) of 3-propyl-1,3-oxazacyclopenane, 11.6 g (0.1 mol) of triethylsilane, and 0.59 g (0.01 mol) reduced nickel. The ampoule is sealed or the reactor is sealed and kept in a thermostat at 130 ° C for 3 hours. After this, 22.0 g of 1-triethyl 512948086 is isolated by vacuum distillation.

siloxy-2- (S, M-methylpropylamino) this aqueous hydroxyamine in the presence of a katana. Yield 95%, kp. PZ Satisers at the same temperature, (10 mm Hg), dl ° 0.8441, characterized in that, 1.438, MRj, 72.40, Ocaque, to increase the yield of the target 71.00. 5product as a derivative

Claims (1)

hydroxyamine use of Z-alkyl-1,3-Formula of the invention oxazacyclopentane, as kata. The method of producing 1-triethylsiloxy-lysator uses reduced 2- (M, M-methylalkylamino) ethanes through a nickel and the process is carried out at 128-interaction of triethylsilane with prod-10132 C in a closed system.