Diethyl Ether → HCID 21356437, compound

Temperature

-78 °C

A solution of lithium diisopropylamine (LDA) in THF was generated by adding 1.5 M methyllithium in diethyl ether (30 mL, 45.0 mmol) to a solution of diisopropylamine (6.4 mL, 45.7 mmol) in 100 mL THF at 0° C. under nitrogen and stirring for 10 min. The solution was then cooled to −78° C., and a solution of (3S)-3-(tosylamino)butano-4-lactone (5.36 g, 21.1 mmol) in 30 mL THF was added dropwise. The resulting yellow solution was stirred for 1 hour at −78° C., and then benzyl bromide (10 mL, 84.1 mmol) was added rapidly. Stirring at −78° C. was continued for 2 hours, and the reaction was quenched with 20 mL sat. aq. NH4Cl solution and allowed to warm to room temperature. The mixture was acidified with 1 M HCl and extracted three times with methylene chloride. The combined organic extracts were dried over Na2SO4 and evaporated to give an orange semisolid that was purified by chromatography (silica gel, hexane/ethyl acetate 3:2) to yield 2.22 g (8.70 mmol, 41%) recovered starting material and 3.37 g (9.76 mmol; 46%) of 4. No diastereomeric addition product could be detected. For further purification 4 can be recrystallized from toluene to give colorless needles. mp. 108.5-109° C., 1H-NMR (300 MHz, CDCl3) δ 7.58 (d, J=8.5 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 7.20 (m, 3H), 6.92 (dd, J=7.7, 1.7 Hz, 2H), 4.97 (d, J=5.5 Hz, 1H), 4.27 (dd, J=7.2, 9.8 Hz, 1H), 3.98 (dd, J=7.2, 9.8 Hz, 1H), 3.65 (m, 1H), 3.00 (m, 1H), 2.77 (m, 2H), 2.46 (s, 3H), 13C-NMR (75.5 MHz, CDCl3) δ 144.27 (C), 138.00 (C), 135.83 (C), 129.89 (CH), 128.97 (CH), 128.88 (CH), 127.10 (CH) 71.25 (CH2) 53.21 (CH), 46.54 (CH), 33.54 (CH2) 21.50 (CH3), EI MS m/e 345.1027 calc. for C18H19NO4S 345.1035.

1. stirringThe resulting yellow solution was stirred for 1 hour at −78° C.
2. stirringStirring at −78° C.
3. waitwas continued for 2 hours
4. customthe reaction was quenched with 20 mL sat. aq. NH4Cl solution
5. temperatureto warm to room temperature
6. extractionextracted three times with methylene chloride
7. dry with materialThe combined organic extracts were dried over Na2SO4
8. customevaporated
9. customto give an orange semisolid that
10. customwas purified by chromatography (silica gel, hexane/ethyl acetate 3:2)
11. customto yield 2.22 g (8.70 mmol, 41%)
12. customrecovered
13. customFor further purification 4
14. customcan be recrystallized from toluene
15. customto give colorless needles

ORD record

ord-5a38a809937644d7aea48ae1e0f82ea3

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772450B2