Ethylamine → HCID 13059394, compound

Temperature

-15 °C

To 14.92 g (100 mmole) of S-methyl-L-cysteine were added 55 ml of water and 21 ml (110 mmole) of triethylamine and the mixture was dissolved in 55 ml of dimethylformamide at room temperature. Thereafter, 26.4 g (110 mmole) of t-butyl-S-4,6-dimethylpyrimidin-2-ylthiol carbanate was added and the mixture was stirred for about 10 hours at room temperature. After addition of 150 ml of water, the mixture was extracted with 2×200 ml of ethyl acetate. The aqueous layer was ice-cooled, adjusted to pH 2 with addition of 6 N hydrochloric acid and extracted with 1×150 ml and 2×80 ml of ethyl acetate. The organic layers were washed with 3×100 ml of 5% hydrochloric acid and 2×100 ml of aqueous saturated sodium chloride and then dried over magnesium sulfate. The solution was concentrated in vacuo to give 24.5 g (98% yield) of S-ethyl-N-butyloxycarbonyl-L-cysteine as an oil. ##STR10## To a solution of 6.23 g (25 mmole) of S-ethyl-N-t-butyloxycarbonyl-L-cysteine dissolved in 60 ml of tetrahydrofuran was added 3.48 ml (25 mmole) of triethylamine. To the resulting mixture cooled to -15° C. was added dropwise 3.28 ml (25 mmole) of isobutyl chloroformate and the mixture was stirred at that temperature for 20 minutes. After cooling to -40° C., 3.2 g of aqueous 70% ethylamine solution (50 mmole) was added in a portion and the mixture was stirred for 2.5 hours under ice cooling. After addition of 70 ml of ethyl acetate, the organic layer was washed successively with 30 ml of aqueous 5% sodium bicarbonate, 2×30 ml of aqueous 10% citric acid, 2×30 ml of aqueous 5% sodium bicarbonate and 2×30 ml of saturated saline and dried over anhydrous magnesium sulfate. The solution was then concentrated in vacuo, resulting in precipitation of crystals, which were recrystallized from ethyl acetate-n-hexane to give 4.93 g of S-ethyl-N-t-butyloxycarbonyl-L-cysteine ethylamide, 71% yield, m.p. 109°-110° C. ##STR11## To 40 ml of ice-cooled 16% solution of hydrogen chloride in ethyl acetate was added dropwise a solution of 2.00 g (7.25 mmole) of S-ethyl-N-t-butyloxycarbonyl-L-cysteine ethylamide in 50 ml of ethyl acetate over 20 minutes. After stirring for 2.5 hours at room temperature, the mixture was concentrated in vacuo and the residual oil was treated with ethyl ether to give 1.31 g (85% yield) of S-ethyl-L-cysteine ethylamide hydrochloride as powder.

1. temperatureAfter cooling to -40° C.
2. stirringthe mixture was stirred for 2.5 hours under ice cooling
3. washthe organic layer was washed successively with 30 ml of aqueous 5% sodium bicarbonate, 2×30 ml of aqueous 10% citric acid, 2×30 ml of aqueous 5% sodium bicarbonate and 2×30 ml of saturated saline
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationThe solution was then concentrated in vacuo
6. customresulting in precipitation of crystals, which
7. customwere recrystallized from ethyl acetate-n-hexane

ORD record

ord-c4642e36dd554454b77f7d14ca19b0d9

Source dataset

uspto-grants-1984_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04440788