C(N[CH:5]([CH3:7])[CH3:6])(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:26])[CH2:16][C:17]1C=CC(SC)=C(Cl)C=1.ICC1CC[O:31][CH2:30]1>O1CCCC1.CN1CCCN(C)C1=O>[CH3:13][O:14][C:15](=[O:26])[CH:16]([CH:6]1[CH2:5][CH2:7][O:31][CH2:30]1)[CH3:17]A solution of diisopropylamine (0.84 mL, 5.98 mmol) in tetrahydrofuran (10 mL) was cooled to −78° C. under an argon atmosphere and then was treated with a 2.5M solution of n-butyllithium in hexanes (2.29 mL, 5.72 mmol). The reaction mixture was stirred at −78° C. for 15 min. At this time, the reaction was slowly treated with a solution of (3-chloro-4-methylsulfanyl-phenyl)-acetic acid methyl ester (prepared as in Example 4, 1.20 g, 5.20 mmol) in tetrahydrofuran (5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.75 mL). The bright yellow solution was allowed to stir at −78° C. for 1 h, after which time, a solution of 3-iodomethyl-tetrahydro-furan (2.21 g, 10.4 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.69 mL) and tetrahydrofuran (5 mL) was added via a cannula. The reaction mixture was then allowed to warm to 25° C., where it was stirred for 48 h. The reaction mixture was then quenched by the addition of a saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (3×30 mL). The organic layers were then combined and washed with a 10% aqueous sulfuric acid solution (25 mL) and a saturated aqueous sodium bicarbonate solution (25 mL). The combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methylsulfanyl-phenyl)-3-(tetrahydro-furan-3-yl-propionic acid methyl ester (663 mg, 41%) as a light yellow oil: EI-HRMS m/e calcd for C15H19ClO3S (M+) 314.0743, found 314.0729.
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