Diisopropylamine → HCID 12067664, compound

Temperature

-78 °C

A solution of diisopropylamine (3.4 mL, 24.38 mmol) in dry tetrahydrofuran (21 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7 mL) cooled to −78° C. was treated with a 2.5M solution of n-butyllithium in hexanes (9.8 mL, 24.38 mmol). The resulting reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3-bromo-4-methylsulfanyl-phenyl)-acetic acid methyl ester (6.10 g, 22.17 mmol) in dry tetrahydrofuran (21 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7 mL). The resulting reaction mixture was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with a solution of iodomethylcyclopentane (5.59 g, 26.60 mmol) in a small amount of dry tetrahydrofuran. The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 15 h. The reaction mixture was quenched with water (300 mL) and then concentrated in vacuo to remove tetrahydrofuran. The remaining aqueous phase was extracted with ethyl acetate (3×150 mL). The combined organic layers 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, 19/1 hexanes/ethyl acetate) afforded 2-(3-bromo-4-methylsulfanyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (4.52 g, 57%) as a light yellow oil: EI-HRMS m/e calcd for C16H21BrO2S (M+) 356.0446, found 356.0435.

1. customThe resulting reaction mixture
2. customThe resulting reaction mixture
3. stirringto stir at −78° C. for 1 h
4. customThe resulting reaction mixture
5. temperatureto warm to 25° C. where it
6. stirringwas stirred for 15 h
7. customThe reaction mixture was quenched with water (300 mL)
8. concentrationconcentrated in vacuo
9. customto remove tetrahydrofuran
10. extractionThe remaining aqueous phase was extracted with ethyl acetate (3×150 mL)
11. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×200 mL)
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-3fd32ae4c05d4e7f82b8788466176c6a

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528543B1