C[C:2]([CH3:11])=[CH:3][CH2:4][O:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9].[C:12]([O-:15])([O-])=[O:13].[Na+].[Na+].[CH:18]([O-])=O.[Na+].[CH3:22][CH2:23]OC(C)=O>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:8]([C:7]1[C:22]2[CH:23]=[C:11]([C:12]([O:15][CH3:18])=[O:13])[CH:2]=[CH:3][C:4]=2[O:5][CH:6]=1)([CH3:9])[CH3:10]
Methyl 4-hydroxy-3-iodobenzoate (6.0 g, 21.5 mmol) is dissolved in DMF (35 ml) in a dry flask under nitrogen and cooled to 0° C. NaH (60% dispersion in oil, 860 mg, 21.5 mmol) is added portion-wise and the reaction is stirred for 1 h, allowing the ice bath to expire. The mixture is then treated with 1-chloro-3-methyl-2-butene (2.67 ml, 23.7 mmol) and NaI (323 mg, 2.15 mmol), and the reaction is stirred for 18 h at RT. The mixture is diluted with EtOAc (150 ml) and washed with 1:1 saturated NaCl/NaHCO3 (100 ml). The organic layer is dried (MgSO4), concentrated to an oil and chromatographed over 700 g slurry-packed silica gel, eluting with 15% EtOAc/hexane. The appropriate fractions are collected and concentrated to afford 5.13 g of a pale oil. The dimethylallyl ether is dissolved in DMF (40 ml) and treated successively with Pd(OAc)2 (165 mg, 0.74 mmol), Na2CO3 (3.9 g, 36.8 mmol), sodium formate (1.0 g, 14.7 mmol), and n-Bu4NCl.H2O (4.5 g, 16.2 mmol). The mixture is stirred for 2 days at 80° C., then diluted with EtOAc (200 ml) and washed with 50% saturated NaCl (3×75 ml) followed by 5% HCl (75 ml). The organic layer is dried (MgSO4), filtered and concentrated to a brown oil. The crude material is chromatographed over 250 g slurry-packed silica gel, eluting with 10% EtOAc/hexane. The appropriate fractions are collected and concentrated to afford 1.33 g (28% over 2 steps) of methyl 3-isopropyl-1-benzofuran-5-carboxylate as an oil. HRMS (FAB) calcd for C13H14O3+H: 219.1021, found 219.1021 (M+H)+.
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