1-Bromo-2-methylpropane → HCID 53673714, compound

Temperature

-78 °C

A solution of freshly prepared lithium diisopropylamide (21.2 mL of a 0.31 M stock solution, 6.14 mmol) cooled to −78° C. was treated with (4-chloro-phenyl)-acetic acid ethyl ester (1.11 g, 5.58 mmol) in tetrahydrofuran/hexamethylphosphoramide (13.9 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. At this time, the reaction was treated with a solution of 1-bromo-2-methyl-propane (1.81 mL, 16.7 mmol) in hexamethylphosphoramide (1 mL). The mixture was stirred at −78° C. for 3 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 16 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL). The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The organics layers dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 2-(4-chloro-phenyl)-4-methyl-pentanoic acid ethyl ester (1.24 g, 87.1%) as a white solid: mp 34-35° C.; EI-HRMS m/e calcd for C14H19ClO2 (M+) 254.1074, found 254.1069.

1. stirringThe mixture was stirred at −78° C. for 3 h
2. temperatureThe reaction was then warmed to 25° C.
3. stirringwas stirred at 25° C. for 16 h
4. customThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL)
5. additionThe reaction mixture was poured into water (100 mL)
6. extractionextracted with ethyl acetate (3×50 mL)
7. dry with materialThe organics layers dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-7f09a12e35924e95a6afd4043ad865cd

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1