[OH:1][CH2:2][C@H:3]1[O:7][C:6](=[O:8])[CH2:5][CH2:4]1.CN(C)CC.C[Si](Cl)(C)C.Br[CH2:20][C:21]1[C:26]([Cl:27])=[CH:25][C:24]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[CH:23][C:22]=1[Cl:35].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].P(=O)(O)(O)O>C1COCC1.O.C(OCC)(=O)C>[Cl:27][C:26]1[CH:25]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH:23]=[C:22]([Cl:35])[C:21]=1[CH2:20][C@@H:5]1[CH2:4][C@@H:3]([CH2:2][OH:1])[O:7][C:6]1=[O:8]Dissolve commercially available (S)-5-hydroxymethyl-dihydro-furan-2-one (33.0 g, 284 mmoles) in 450 mL of THF, and then add 31.2 g (427 mmoles) of dimethylethylamine along with 50 mL of THF (rinse). Place the mixture under nitrogen and cool in an ice/water bath. Add trimethylsilyl chloride 39.8 mL (313 mmoles) while maintaining the temperature below 13° C. Filter the mixture and rinse the cake with THF (2×100 mL). Cool the solution of TMS (trimethylsilyl) protected lactone to −78° C. and add 4-bromomethyl-3,5-dichloro-4′-fluoro-biphenyl (71.2 g, 213 mmoles). Add a 1 M solution of lithium hexamethyldisilazide in THF (264 mL, 264 mmoles) over 1 h at −65 to −78° C. After stirring for 1 h, add a 600 mL solution of 120 mL of conc. phosphoric acid in water. After stirring for 10 min at room temperature, add 1 L of ethyl acetate and stir the mixture for 10 min. The layers separate. Wash the organic layer with water (2×500 mL). Evaporate the solvent down to a solution of approximately 250 mL and add an additional 250 mL of EtOAc. Evaporate the solvent until a solution of approximately 300-350 mL remains. Heat the mixture to reflux and add 494 mL of heptane. Allow the slurry to cool to room temperature, collect the solids by filtration, and rinse with heptane (2×100 mL). Dry the solid under vacuum to afford 62.1 g (59%) of the titled compound. MS (m/z): 369 (M+1, 35Cl), 371 (M+1, 37Cl).
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