Cl.[CH:2]1([N:6]([C@@H:10]2[CH2:15][C:14]3[C:16]([O:21]C)=[CH:17][CH:18]=[C:19]([F:20])[C:13]=3[O:12][CH2:11]2)[CH:7]([CH3:9])[CH3:8])[CH2:5][CH2:4][CH2:3]1.B(Br)(Br)Br.C(Cl)(Cl)Cl>C(Cl)Cl>[CH:2]1([N:6]([C@@H:10]2[CH2:15][C:14]3[C:16]([OH:21])=[CH:17][CH:18]=[C:19]([F:20])[C:13]=3[O:12][CH2:11]2)[CH:7]([CH3:9])[CH3:8])[CH2:3][CH2:4][CH2:5]1(R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran hydrochloride (1.76 g, 5.34 mmol) was dissolved in anhydrous CH2Cl2 (45 mL) and cooled to -40° C. To the solution was BBr3 (1.3 mL, 13.4 mmol), dissolved in anhydrous CH2Cl2 (7 mL), added dropwise. The cooling-bath was removed and after 2 h at room temperature the reaction was complete. The reaction was poured out onto an ice/2M NH3 solution and the CH2Cl2 portion was separated, the aqueous layer re-extracted, twice, with CH2Cl2. The combined CH2Cl2 portions were dried (MgSO4), filtered, and the solvent removed in vacuo to give the crude residue. Chromatography on silica (eluent: 30% ethyl acetate/hexane) gave 1.46 g (98% yield) of the title compound as a gum [α]21D =-95.7° (C=0.1; CHCl3) GC-MS (70 eV) M=279 (0.7%). The hydrochloride salt was made by dissolving the pure base in ether and dropping an excess of an ethereal HCl solution. The salt was washed with diethyl ether to give a white solid Mp: 120° C. sinters.
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