反应详情

The title compound of Example 24 (6.77 g, 24.26 mmol) was placed in a Parr bottle containing 220 ml absolute EtOH and 10.0 g (wet) Raney nickel catalyst that had been previously shaken under hydrogen (40 psi) for 10 minutes. The mixture was shaken under hydrogen (40 psi) for an hour, filtered over celite, and the filtrate was concentrated to a yellow-white solid that was dried under vacuum overnight. This solid was stirred in 1,2-dichloroethane (250 ml) at 0° C. Acetic anhydride (30 ml) was added, followed by formic acid (30 ml), dropwise under nitrogen. The resulting mixture was stirred at room temperature for 2 hours, concentrated to half the original volume; and azeotroped with toluene to remove residual formic/acetic acid. The crude solid was triturated with methanol to give the title compound (4.92 g, 73%) as an off-white solid; m.p. 206°-209° C. (dec); 'H-NMR (DMSO-d6) δ 1.08 (d, J=6.8 Hz, 6.0 (CH3)2CH), 2.74 (m, J=6.8 Hz, 1.0 (CH3)2CH), 8.18 (d, J=10.3 Hz) and 10.26 (br s) [total 1.0, NHCHO from two conformers], 11.17 (br s, 1.0).

1. stirringThe mixture was shaken under hydrogen (40 psi) for an hour
2. filtrationfiltered over celite
3. concentrationthe filtrate was concentrated to a yellow-white solid
4. customthat was dried under vacuum overnight
5. stirringThis solid was stirred in 1,2-dichloroethane (250 ml) at 0° C
6. additionAcetic anhydride (30 ml) was added
7. stirringThe resulting mixture was stirred at room temperature for 2 hours
8. concentrationconcentrated to half the original volume
9. customand azeotroped with toluene
10. customto remove residual formic/acetic acid
11. customThe crude solid was triturated with methanol