C[C:2]1[C:3]([O:13][CH3:14])=[C:4]([CH:8]=[C:9]([F:12])[C:10]=1[OH:11])[C:5]([OH:7])=[O:6].[C:15]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:34]1[CH:39]=[CH:38][C:37]([C@@H:40](O)[CH3:41])=[CH:36][CH:35]=1>C1COCC1>[F:12][C:9]1[C:10]([O:11][C@H:40]([C:37]2[CH:38]=[CH:39][N:34]=[CH:35][CH:36]=2)[CH3:41])=[CH:2][C:3]([O:13][CH3:14])=[C:4]([CH:8]=1)[C:5]([O:7][CH3:15])=[O:6]A stirred solution of methyl 5-fluoro-2-methoxy-4-hydroxybenzoic acid (250 mg, 1.25 mmol, see Scheme II) in THF (15 mL) was treated with triphenylphosphine (494 mg, 1.88 mmol) and cooled to 0° C. under Argon. To this was added, dropwise over a period of 1 h, a solution of (S)-(-)-1-(4-pyridyl)-ethanol (232 mg, 1.88 mmol) and N,N'-diethylazodicarboxylate (300 μL, 1.88 mmol) in THF (5 mL). The reaction was allowed to warm to ambient temperature overnight with stirring. The reaction was filtered and the solvent was removed under reduced pressure. The residue was chromatographed on a silica gel column packed in 1:1 CH2Cl2 :EtOAc and elated with same. The appropriate fractions were combined and the solvent removed under reduced pressure to afford an impure mixture of 5-fluoro-2-methoxy-4-[1-(S)-(4-pyridyl)ethoxylbenzoate. The residue was rechromatographed on a preparative HPLC using a gradient of 95:5 to 5:95 water:acetonitrile (0.1% TFA added). The appropriate fractions were combined and the solvent removed under reduced pressure to afford the methyl 5-fluoro-2-methoxy-4-[1-(S)-(4-pyridyl)ethoxy]benzoate.
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