Bis(2-chloroethyl)amine hydrochloride → N,N-bis(2-chloroethyl)-(R)-alanine ethyl ester

A suspension of bis(2-chloroethyl)amine hydrochloride (0.392 g; 2.1 mmol) in 5N aqueous sodium hydroxide (3 mL) is extracted with ether (2×10 mL) and the combined extracts are washed with a minimum amount of water and saturated brine. The ethereal solution is dried quickly over magnesium sulfate and filtered. Tetrahydrofuran (2 mL) is added to the filtrate, and ether is carefully removed under reduced pressure on a rotavapor unit without heating. The residue is mixed with a solution of ethyl (S)-2-[(methylsulfonyl)oxy]-propionate (0.5 g; 2 mmol) in tetrahydrofuran (1 mL). After stirring the reaction mixture for 24 hrs at room temperature, there is no visible precipitate. The volatiles are removed under reduced pressure and the remaining viscous oil is dissolved in ether (8 mL), and the slightly turbid solution is filtered after 60 minutes. The filtrate is treated dropwise with n-heptane to induce crystallization; the final ratio of n-heptane/ether is 1:3. The crystalline salt is collected by filtration and washed quickly with a small portion of ether. There is obtained 0.653 g (yield 83.3%) of N,N-bis(2-chloroethyl)-(R)-alanine ethyl ester, trifluoromethanesulfonate; mp 73-74.5° C.; 1H NMR (300 MHz, CDCl3) δ 1.35 (t, J=7.1 Hz, 3H), 1.76 (d, J=7.2 Hz, 3H), 3.87 (m, 2H), 4.00 (m, 2H), 4.35 (q, J=7.1 Hz, 2H), 4.57 (q, J=7.2 Hz, 1H), 9.02 (b, 1H).

1. extractionis extracted with ether (2×10 mL)
2. washthe combined extracts are washed with a minimum amount of water and saturated brine
3. dry with materialThe ethereal solution is dried quickly over magnesium sulfate
4. filtrationfiltered
5. additionTetrahydrofuran (2 mL) is added to the filtrate, and ether
6. customis carefully removed under reduced pressure on a rotavapor unit
7. temperaturewithout heating
8. customThe volatiles are removed under reduced pressure
9. dissolutionthe remaining viscous oil is dissolved in ether (8 mL)
10. filtrationthe slightly turbid solution is filtered after 60 minutes
11. additionThe filtrate is treated dropwise with n-heptane
12. customcrystallization
13. filtrationThe crystalline salt is collected by filtration
14. washwashed quickly with a small portion of ether

ORD record

ord-b8d3806768d74fa4a177a9d297c67ee5

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07019137B2