[OH:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.[C:22]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C.C(OCC)(=O)C>[OH:1][C@@H:2]1[C@@H:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:22])=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1
To a solution of (3R,4R)-tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate (490 mg, 1.67 mmol, procedure from WO 2000/63173) in DMF (6 mL) was added K2CO3 (577 mg, 4.2 mmol) followed by methyl iodide (0.52 mL, 8.4 mmol) at rt. The mixture was stirred at rt for 18 h. It was then diluted with 50 mL ethyl acetate and the solids were removed by filtration. The solvent was then evaporated under vacuum and the residue was purified via silica gel chromatography (hexanes-100% EtOAc) to yield (3R,4R)-tert-butyl 3-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate (450 mg, 88% yield). LCMS (method T) RT 3.068 min, m/z 306.3 (M−H)−; 1H NMR (500 MHz, chloroform-d) δ 7.15 (d, J=8.7 Hz, 2H), 6.87 (d, J=8.7 Hz, 2H), 4.40-4.30 (m, 1H), 4.25-4.05 (m, 1H), 3.78 (s, 3H), 3.64-3.52 (m, 1H), 2.77-2.66 (m, 1H), 2.65-2.51 (m, 1H), 2.45 (br. s., 1H), 2.26-2.10 (m, 1H), 1.76 (d, J=2.7 Hz, 1H), 1.71-1.60 (m, 1H), 1.48 (s, 9H).
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