[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[CH:5][C:6]2[S:10][CH:9]=[N:8][C:7]=2[CH:11]=1.C([Li])CCC.[CH3:19][C:20]([CH3:24])([CH3:23])[CH:21]=[O:22].O>O1CCCC1.CCCCCC>[CH3:19][C:20]([CH3:24])([CH3:23])[CH:21]([C:9]1[S:10][C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:12])[F:13])=[CH:11][C:7]=2[N:8]=1)[OH:22]To a stirred solution of 3.8 g (19.0 mmol) of 5-(trifluoromethyl)-1,3-benzothiazole in 30 mL of tetrahydrofuran at −78° C. was added 13.1 mL (21.0 mmol) of a 1.6 M solution of n-butyllithium in hexane over 45 min. Then, 1.8 g (21.0 mmol) of trimethylacetaldehyde in 10 mL of tetrahydrofuran was added dropwise over 30 min. The reaction mixture was stirred for 1 h at −78° C., and then allowed to warm to 0° C. Then, 25 mL of water was added and the mixture was extracted with 80 mL of ether. The ether was washed with 40 mL of water (3×), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with ethyl acetate:hexane (1:9) to afford 1.8 g (33%) of 2,2-dimethyl-1-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]-1-propanol as an off-white solid. The enantiomers were separated in 98.8% ee using a Chiralpak AD, 10 micron column with a mobile phase of 90% carbon dioxide: 10% methanol and a flow rate of 2.0 mL/minute. 1H-NMR (400MHz, DMSO-d6): δ 8.33–8.29 (m, 2H), 7.71 (d, J=8 Hz, 1H), 6.61 (d, J=5 Hz, 1H), 4.60 (d, J=5 Hz, 1H), 0.97 (s, 9H).
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