Diisopropylamine → HCID 49875539, compound

Temperature

-78 °C

Diisopropylamine (17.92 mL, 128 mmol) was dissolved in THF (300 mL) and stirred at −30° C. while BuLi (8.91 g, 139 mmol) was added dropwise. The mixture was stirred at the same temperature for 0.5 h. Then the mixture was cooled to −78° C. and 4-bromothiophene-3-carboxylic acid (12 g, 58.0 mmol) and HMPA (2.02 mL, 11.6 mmol) dissolved in anhydrous THF (200 mL) were added slowly. The mixture was stirred at the same temperature for 1 h. Then the reaction mixture was purged with an excess of gaseous CO2 at −40° C. The resulting solution was stirred at RT for about 15 min and then quenched with H2O. 10% aq. NaOH was added. The aqueous layer was separated and washed with EtOAc. The aqueous layer was acidified with 10% aq. HCl to pH 1˜2 and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (11 g, 43.8 mmol, 76% yield) as white solid, which was used in the next step (example 1.2.3) without further purification. LC-MS (Method A): m/z 273 (M+Na)+, Rt: 0.58 min.

1. additionwas added dropwise
2. additionwere added slowly
3. stirringThe mixture was stirred at the same temperature for 1 h
4. customThen the reaction mixture was purged with an excess of gaseous CO2 at −40° C
5. stirringThe resulting solution was stirred at RT for about 15 min
6. customquenched with H2O
7. addition10% aq. NaOH was added
8. customThe aqueous layer was separated
9. washwashed with EtOAc
10. extractionextracted with ethyl acetate (3×200 mL)
11. washThe combined organic layers were washed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure

ORD record

ord-97c0f5a704f040caa1776ff6d30cb102

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200005B2