4-Toluenesulfonyl chloride → tert-butyl N-{3-[(2-methyl-1H-imidazol-1-yl)methyl]phenyl}carbamate

Participants

Reaction Conditions

Reaction Steps

1-[3-[(tert-Butoxycarbonyl)amino]phenyl]methanol (10 g, 44.8 mmoles) (Ref.: F. J. Brown, P. R. Bernstein, L. A. Cronk, D. L. Dosset, K. C. Hebbel. T. P. Maduskuie, Jr., H. S. Shapiro, E. P. Vacek, Y. K. Lee, A. K. Willard, R. D. Krell and D. W. Snyder, J. Med. Chem., 32, 1989, 807-826) (10 g, 44.8 mmoles) was dissolved in anhydrous pyridine (51 mL) and the solution was cooled to 0° C. p-Toluenesulfonyl chloride (10.25 g, 53.7 mmoles) was added and the mixture was stirred at 0° C. for 2.5 h under argon. The pyridine was azeotroped off with toluene at 51° C. and the residue was taken up in anhydrous DMF (50 mL). 2-Methylimidazole (4.05 g, 49.3 mmoles) was dissolved in anhydrous DMF (123 mL) and 95% sodium hydride (1.24 g, 49.3 mmoles) was added in portions over 20 min to the stirred solution under argon at 25° C. The mixture was stirred at 25° C. for 1.5 h. The title tosylate above in anhydrous DMF was added dropwise over 15 min and the mixture was stirred at 25° C. for 2.5 h. The solution was evaporated to dryness and the residue was chromatographed on silica gel using 0.25%.2.5% (10% conc. NH4OH in methanol)-dichloromethane as the eluant to give the title compound (0.8412 g, 6.5%): FABMS: m/z 288.3 (MH+); HRFABMS: m/z 526.3036 (MH+), Calcd. C28H40N5O5: m/z 526.3029; δH (CDCl3) 1.50 (9H, s, CH3), 2.34 (3H, s, 2-CH3), 5.02 (2H, s, CH2-Im), 6.67 (1H, d, Ar—H4), 6.84 (1H, s, Im-H5), 6.95 (1H, s, Im-H4), 7.19 (1H, s, Ar—H2) and 7.28 ppm (2H, m, Ar—H5 and Ar—H6); δC (CDCl3) CH3: 13.0, 28.4, 28.4, 28.4; CH2: 49.8; CH: 116.6, 118.0, 120.1, 121.0, 127.0, 129.7; C, 80.7, 137.2, 139.3, 145.0, 152.8.

Provenance & Evidence