[CH3:1][C@@H:2](OS(C)(=O)=O)[C:3]#[CH:4].[Cl:10][CH2:11][C:12]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])=[O:13].C([Zn]CC)C.Cl>O1CCCC1.C1(C)C=CC=CC=1.[Pd](Cl)Cl.CC(CC#N)=N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(=O)C)C>[Cl:10][CH2:11][C@@:12]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])([OH:13])[C@@H:3]([CH3:4])[C:2]#[CH:1]887.3 mg (3.423 mmol) of palladium(II)-dichloride-diacetonitrile were dissolved in 325.0 ml of tetrahydrofuran. 2.243 g (8.530 mmol) of triphenylphosphine were added. The reaction mixture turned yellow and, after 6 minutes, turbid. The reaction mixture was stirred for 10 minutes at room temperature, whereafter 22.81 g (153.9 mmol) of (R)-methanesulfonic acid 1-methyl-prop-2-ynylester and 16.30 g (85.52 mmol) of 2-chloro-1-(2,5-difluoro-phenyl)-ethanone were added together with about 25 ml of totally 233.3 ml (256.6 mmol) of diethylzinc solution in toluene (1.1 M) dropwise. The temperature was permitted to rise to 36° C. The remaining diethylzinc solution was added dropwose within 12 minutes at 37–38° C., whereafter the temperature was prevented from rising over 39° C. After 40 minutes (temperature about 27° C.) the reaction mixture was poured onto 350 ml of ice-cold half-saturated aqueous sodium chloride solution, 500 ml of ethylacetate were added, the mixture was stirred for 5 minutes at room temperature, and 70 ml of 25% aqueous hydrochloric acid were added (everything in solution). The aqueous phase was washed once with 250 ml of ethyl acetate and the organic phases once with 150 ml of quarter-saturated aqueous sodium bicarbonate solution and once with 50 ml of 0.1N aqueous hydrochloric acid. The organic phases were combined, dried over sodium sulfate and evaporated to dryness. 24.85 g of (2R,3S)-1-chloro-2-(2,5-difluoro-phenyl)-3-methyl-pent-4-yne-2-ol were obtained, which were 70.5% pure and contained 86% of the stated diastereomer. Yield 83.1%.
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