反应详情

温度

50 °C

Example 48(a) was prepared in a similar manner as Example 41(a) from the starting material described below. 1H NMR (300 MHz, CD3OD) δ 8.54 (d, 1H, J=4.8 Hz), 7.95 (d, 1H, J=9.49 Hz), 7.84 (td, 1H, 1=7.71 Hz, =1.78 Hz), 7.70 (d, 1H, J=7.95 Hz), 7.53 (d, 1H, J=16.59 Hz), 7.40 (d, 1H, J=7.92 Hz), 7.29 (qd, 1H, 1=7.45 Hz, J=1.07 Hz), 7.11 (d, 1H, 1=11.8), 7.03-7.06 (m, 2H), 6.71 (s, 1H), 4.50 (q, 2H, J=7.16 Hz), 2.27 (s, 3H), 2.26 (s, 3H), 1.38 (t, 3H, 1=7.11 Hz). MS (ESI+) [M+H]/z Calc'd 496, found 496. Anal. Calc'd: C, 67.86; H, 5.29; N, 19.79. Found: C, 66.24; H, 5.50; N, 18.61. The starting material was prepared as follows: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MEOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). To a solution of carbonic acid 4-nitro-phenyl ester 2-trimethylsilanyl-ethyl ester (566 mg, 2 mmol) in DMF (4 ml) at 23° C. under an atmosphere of argon was added DMAP (12 mg. 0.1 mmol), DIEA (0.35 ml, 2 mmol) and 4-fluoro-6-methyl-benzene-1,3-diamine. The resulting solution was heated to 50° C. for 48 h. The reaction mixture was quenched with saturated NaHCO3 (aq), extracted with EtOAc (3×20 ml). The EtOAc was removed in-vacuo, and the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine, dried with Na2SO4, filtered and concentrated. Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane) gave (5-amino-4-fluoro-2-methyl-phenyl)carbamic acid 2-trimethylsilanyl-ethyl ester (160 mg, 28%). MS (ESI+) [M+H]/z Calc'd 634, found 634.

1. customThe reaction mixture was quenched with saturated NaHCO3 (aq)
2. extractionextracted with EtOAc (3×20 ml)
3. customThe EtOAc was removed in-vacuo
4. dissolutionthe residue was re-dissolved in Et2O
5. washthen washed with 3 N NaOH (aq), water, brine
6. dry with materialdried with Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane)