[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[CH:14][C:10]=2[C:11](O)=[O:12])[CH2:3]1.[BH4-].[Na+].II>C1COCC1>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([C:9]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[CH:14][C:10]=2[CH2:11][OH:12])[CH2:5]1To a stirred and ice-bath cooled solution of 2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzoic acid (Intermediate 1, 27.0 g, 99.6 mmol) in THF (250 mL) was added sodium borohydride (12.56 g, 358.6 mmol) in small portions, followed by iodine (32.5 g, 139.4 mmol) in THF (250 mL). The addition was carried out such that the temperature maintained below 10° C. The mixture brought to room temperature and refluxed for 12 hours. It was cooled and then quenched with methanol (250 mL). Solvents were evaporated and the residue treated with 2M NaOH (500 mL) for 2 hours. The aqueous layer extracted with ethyl acetate (3×150 mL), and the combined organic phases were washed with water and brine before being dried (Na2SO4) and concentrated to give the title compound as a gummy solid. MS (ES) MH+: 257.2 for C13H17F2NO2
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