[F:1][C:2]1[CH:3]=[C:4]([C@:9]2([OH:17])[O:14][CH2:13][C@@H:12]([CH3:15])[NH:11][C@H:10]2[CH3:16])[CH:5]=[C:6]([F:8])[CH:7]=1.[BH4-].[Na+].Cl>C(O)C.O.O>[OH:14][CH2:13][C@H:12]([NH:11][C@@H:10]([CH3:16])[C@@H:9]([C:4]1[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=1)[OH:17])[CH3:15]The hydrobromide salt of (2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol (0.023 mole) (U.S. Pat. No. 5,104,870) is dissolved in a 50:50 mixture of ethanol/water (150 mL) and chilled to 0° C. while being stirred under a nitrogen atmosphere. A solution of sodium borohydride (0.093 mole) in water (25 mL) is added dropwise, and the solution is allowed to warm to room temperature while being stirred overnight. The solution is cooled to 0° C., and concentrated hydrochloric acid (25 mL) is carefully added dropwise. The mixture is concentrated under reduced pressure to remove ethanol and then diluted with water to dissolve the solids. This solution is cooled with an ice bath, made basic by treatment with 40% aqueous sodium hydroxide and extracted three times with diethyl ether. The combined ether extracts is washed with a saturated sodium chloride solution, dried over sodium sulfate and spin evaporated in vacuo to give the free base of (rac)-(R*,S*)-2-((2-hydroxy-(R)-1-methylethyl)amino)-1-(3,5-difluorophenyl)propanol (21). A sample of the free base is treated with ethereal hydrogen chloride to give a solid that may be recrystallized from ethanol/ether to give the hydrochloride salt of (rac)-(R*,S*)-2-((2-hydroxy-(R)-1-methylethyl)amino)-1-(3,5-difluorophenyl)propanol. See eg., Boswell et al., J. Heterocyclic Chem., (1996) 33:33.
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