Furan, 2-(bromomethyl)tetrahydro- → HCID 21958994, compound

Temperature

-78 °C

A solution of freshly prepared lithium diisopropylamide (23 mL of a 0.31 M stock solution, 7.13 mmol) cooled to −78° C. was treated with (3,4-dichloro-phenyl)-acetic acid (696 mg, 3.39 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (8.5 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 2-bromomethyl-tetrahydro-furan (672 mg, 4.07 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL). The reaction mixture was stirred at −78° C. for 2 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 18 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution. The excess solvent was removed in vacuo. The residue was diluted with water (50 mL) and was treated with a 1N aqueous hydrochloric acid solution until the solution was acidic. The resulting solution was extracted into ethyl acetate (3×50 mL). The organics were washed with a saturated aqueous lithium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 50/50 hexanes/ethyl acetate with glacial acetic acid) afforded 2-(3,4-dichloro-phenyl)-3-(tetrahydro-furan-2-yl)-propionic acid (692.3 mg, 70.8%) as a white solid: mp 100–102° C.; FAB-HRMS m/e calcd for C13H14Cl2O3 (M+H)+ 289.0399, found 289.0404.

1. stirringThe reaction mixture was stirred at −78° C. for 2 h
2. temperatureThe reaction was then warmed to 25° C.
3. stirringwas stirred at 25° C. for 18 h
4. customThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution
5. customThe excess solvent was removed in vacuo
6. additionThe residue was diluted with water (50 mL)
7. additionwas treated with a 1N aqueous hydrochloric acid solution until the solution
8. extractionThe resulting solution was extracted into ethyl acetate (3×50 mL)
9. washThe organics were washed with a saturated aqueous lithium chloride solution (1×100 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-a7d4c2f19f074d7384397d52c05243ae

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2