Diisopropylamine → 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed tetrahydrofuran (15 mL) and diisopropyl amine (357 μL, 2.55 mmol) and it was cooled to −78° C. in a dry ice/acetone bath. To this cooled solution was then added n-butyl lithium (2.5 M solution in hexanes, 970 μL, 2.43 mmol) and it was stirred for 15 min at −78° C. To this cooled solution was then added a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in PCT WO 2003/095438 A1, Example 4, 511 mg, 2.21 mmol) in tetrahydrofuran (5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL) dropwise. This was then stirred for one hour at −78° C. After such time, 2(R)-iodomethyl-tetrahydro-furan (657 mg, 3.1 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL) was added dropwise at −78° C. The reaction was then allowed to slowly warm to 25° C. and it was stirred for 16 h. After such time, the reaction was quenched with a saturated aqueous ammonium chloride solution (20 mL) and then extracted with ethyl acetate (3×20 mL). The organics were dried over magnesium sulfate, filtered and then concentrated in vacuo. Purification on an AnaLogix Intelliflash system (40 g column, 5% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-2(R)-yl)-propionic acid methyl ester (237 mg, 34%) as a reaction of two diastereomers which was a light yellow oil: ES-HRMS m/e calcd for C15H19O3SCl (M+Na)+ 337.0635, observed 337.0635.

Provenance & Evidence