Diisopropylamine → 2-Bromo-5-fluoro-4-(triethylsilyl)pyridine

온도

-75 °C

A solution of diisopropylamine (25.3 g, 250 mmol) in 370 ml THF was cooled with a dry-ice acetone bath at −75° C. BuLi (100 ml, 250 mmol, 2.5 M in hexanes) was added dropwise while maintaining the temperature below −50° C. After the temperature of the mixture had reached −75° C. again, a solution of 2-bromo-5-fluoropyridine (36.7 g, 208 mmol) in 45 ml THF was added dropwise. The mixture was stirred for 1 h at −75° C. Triethylchlorosilane (39.2 g, 260 mmol) was added quickly. The temperature stayed below −50° C. The cooling bath was removed and the reaction mixture was allowed to warm to −15° C., poured onto aq. NH4Cl (10%). TBME was added and the layers were separated. The organic layer was washed with brine, dried with MgSO4.H2O, filtered and evaporated to give a brown liquid which was distilled at 0.5 mm Hg to yield the title compound as a slightly yellow liquid (b.p. 105-111° C.). HPLC: RtH11=2.284 min; ESIMS: 290, 292 [(M+H)+, 1Br]; 1H-NMR (400 MHz, CDCl3): 8.14 (s, 1H), 7.40 (d, 1H), 1.00-0.82 (m, 15H).

1. temperaturewhile maintaining the temperature below −50° C
2. customhad reached −75° C.
3. customstayed below −50° C
4. customThe cooling bath was removed
5. temperatureto warm to −15° C.
6. additionpoured onto aq. NH4Cl (10%)
7. additionTBME was added
8. customthe layers were separated
9. washThe organic layer was washed with brine
10. dry with materialdried with MgSO4.H2O
11. filtrationfiltered
12. customevaporated
13. customto give a brown liquid which
14. distillationwas distilled at 0.5 mm Hg

ORD 기록

ord-350844ae501c4a7a841aae53aadc3766

출처 데이터셋

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08865712B2