[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=O.[CH2:12]([Mg]Br)[CH3:13].[CH3:16][CH2:17]OCC.Cl.[OH-].[Na+].C(N1C=CN=C1)(N1C=CN=C1)=[O:25]>C1COCC1.C(OCC)(=O)C>[CH2:16]([C:4]1([CH2:12][CH3:13])[O:6][C:7](=[O:25])[NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[CH:8][C:3]1=2)[CH3:17]A solution of methyl 2-amino-benzoate (15.1 grams (g), 100 millimoles (mmol)) in dry THF (200 milliliters (mL)) was treated at −78° C. under nitrogen with a solution of ethylmagnesium bromide in ether (3.0 M, 133 mL, 399 mmol). The reaction mixture was slowly warmed to ambient temperature, kept stirring for 2 hours under nitrogen and then poured into a cold 1 N aqueous hydrochloride solution (500 mL). The mixture was neutralized with aqueous 1 N sodium hydroxide solution and ethyl acetate (500 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried (MgSO4). After removal of solvent in vacuo, the residue was taken up in anhydrous THF (200 mL) and used in the next step without further purification. To this solution was added 1,1′-carbonyldiimidazole (23.25 g, 150 mmol) under nitrogen. The reaction solution was heated at 50° C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution washed with 1N aqueous hydrochloride solution (2×40 mL), brine (20 mL), and dried with MgSO4. After removal of solvent in vacuo, the residue was triturated with diethyl ether to give the title compounds as white solid (14.8 g, 72%, mp 159-160° C.). 1H NMR (CDCl3): δ 8.40 (s, 1H), 7.22 (td, J=7.3, 1.6 Hz, 1H), 7.05 (td, J=7.8, 1.0 Hz, 1H), 7.02 (dd, J=7.7, 1.3 Hz, 1H), 6.80 (d, J=7.7 Hz, 1H), 1.98 (m, 4H), 0.89 (t, J=7.3 Hz, 6H); MS (EI) m/z 205; Anal. calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 69.88; H, 6.99; N, 6.31.
Loading…
