Cl[Si](C)(C)C.Br[C:7]([F:14])([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9].N1([CH2:24][NH:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)C2C=CC=CC=2N=N1>O1CCCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[C:7]([F:14])([F:13])[CH2:24][NH:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)[CH3:12]To a mixture of 12.1 g (0.185 g-atom) of zinc powder (−325 mesh) and 160 mL of anhydrous tetrahydrofuran was added 17.6 mL (0.14 mole) of chlorotrimethylsilane in one portion. After stirring for 20 minutes, a solution of 17.8 mL (0.14 mole) of ethyl bromodifluoroacetate in 20 mL of tetrahydrofuran was added dropwise at a rate to keep the internal temperature below 35 degrees. The mixture was stirred for 20 minutes and then cooled to −10 to 0 degrees. A solution of 20 g (0.093 mole) of benzotriazol-1-ylmethyl-cyclopentylamine in 80 mL of tetrahydrofuran was added dropwise at a rate to keep the internal temperature at −10 to 0 degrees. After 10 minutes the reaction mixture was warmed to room temperature and stirred for 3 hours at room temperature. The solution was cooled to −10 to 0 degrees and quenched by the addition of saturated aqueous sodium bicarbonate at a rate to maintain the internal temperature −10 to 0 degrees. Ether was added, the mixture was stirred for 15 minutes at room temperature and then filtered through Celite, washing with ether. The filtrate was extracted 3 times with ether. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Ether and hexane were added to the residue, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was then distilled under vacuum to give 12.4 g of 3-cyclopentylamino-2,2-difluoropropionic acid ethyl ester as a colorless oil. bp 75-82 degrees at 1 mm Hg.
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