COC[O:4][C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7]([O:12][CH2:13][O:14][CH3:15])[C:6]=1[C:16]1([C:19](OCC)=[O:20])[CH2:18][CH2:17]1.O.[H-].[Na+].C(Cl)OC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C(O)C>[OH:20][CH2:19][C:16]1([C:6]2[C:7]([O:12][CH2:13][O:14][CH3:15])=[CH:8][CH:9]=[C:10]([CH3:11])[C:5]=2[OH:4])[CH2:17][CH2:18]1To a solution of ethyl 1-[2,6-bis(methoxymethoxy)-3-methyl-phenyl]cyclopropanecarboxylate (Intermediate 153, 300 mg, 0.93 mmol) in ethanol (10 ml) HCl 6N in water (0.4 mL, 2.4 mmol) was added and the reaction mixture was stirred overnight at 50° C. Combined solvents were removed under reduced pressure. The residue was suspended in dry toluene (10 mL) and the solvent evaporated. The obtained residue was dissolved in dry tetrahydrofuran (10 ml), the mixture was cooled to 0° C. and NaH (60% dispersion in mineral oil) (80 mg, 2 mmol) was added and the reaction mixture was stirred for 30 minutes at the same temperature. MOM-Cl (0.083 mL, 1.1 mmol) was then added and the reaction mixture was stirred for 1 hour at 0° C. LiAlH4 (1M in THF, 1.2 ml, 1.2 mmol) was added and the reaction mixture was further stirred for 1 hour at the same temperature. The reaction was quenched with an aqueous saturated solution of ammonium chloride (10 ml), diluted with water (20 ml) and extracted with ethyl acetate (2×50 ml). Combined organic layers were dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluents affording the title compound (70 mg) as a white solid.
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