Diisopropylamine → 3-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid

Temperature

-78 °C

A solution of diisopropylamine (17.1 mL, 122.21 mmol) in dry tetrahydrofuran (55 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (18 mL) was cooled to −78° C. under nitrogen and then treated with a 10M solution of n-butyllithium in hexanes (12.2 mL, 122.21 mmol). The yellow reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of 4-iodophenylacetic acid (15.25 g, 58.19 mmol) in dry tetrahydrofuran (55 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (18 mL). The reaction mixture turned dark in color and was allowed to stir at −78° C. for 45 min, at which time a solution of iodomethylcyclopentane (13.45 g, 64.02 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25° C. where it was stirred for 42 h. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran and then quenched with a 10% aqueous hydrochloric acid solution (100 mL). The resulting aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-iodo-phenyl)-propionic acid (13.97 g, 70%) as a cream solid: mp 121-122° C.; EI-HRMS m/e calcd for C14H17IO2 (M+) 344.0273, found 344.0275.

1. additionwas added dropwise
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 42 h
4. concentrationThe reaction mixture was concentrated in vacuo
5. customto remove tetrahydrofuran
6. customquenched with a 10% aqueous hydrochloric acid solution (100 mL)
7. extractionThe resulting aqueous layer was extracted with ethyl acetate (3×200 mL)
8. washThe combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×200 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-249fa6ac44024c7d95ed61cb8a641113

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06384220B2