[OH:1][CH2:2][C@@H:3]1[CH2:6][CH2:5][C@H:4]1[C:7]([O:9][CH3:10])=[O:8].[F:11][C:12]([F:20])(S(F)(=O)=O)C(O)=O.C([O-])(O)=O.[Na+]>C(#N)C>[F:11][CH:12]([F:20])[O:1][CH2:2][C@@H:3]1[CH2:6][CH2:5][C@H:4]1[C:7]([O:9][CH3:10])=[O:8]To a solution of (1R,2R)-methyl 2-(hydroxymethyl)cyclobutanecarboxylate (100 mg, 0.694 mmol) in acetonitrile (5 mL) was added CuI(I) (66.1 mg, 0.347 mmol) and the reaction mixture was heated to 60° C. To the stirred solution was added 2,2-difluoro-2-(fluorosulphonyl)acetic acid (124 mg, 0.694 mmol) and the reaction mixture was stirred for an additional 12 h at 60° C. The reaction mixture was cooled to 0° C., a saturated aqueous solution of NaHCO3 was added and extracted with ethyl acetate (3×10 mL) The combined organic layer was dried over Na2SO4, filtered and the filtrate evaporated under reduced pressure to afford Intermediate 241A as a yellow oil (100 mg, 80%). The crude product was used in the next step without further purification. 1H NMR (300 MHz, chloroform-d) δ ppm 5.92-6.56 (m, 1H), 3.86 (d, J=5.29 Hz, 2H), 3.70 (s, 3H), 3.01 (d, J=8.88 Hz, 2H), 2.18 (d, J=10.15 Hz, 2H), 1.68-2.02 (m, 2H).
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