反应详情

To a solution of intermediate 132, dimethyl-carbamic acid 2-cyano-5-fluoro-phenyl ester, (340 mg, 1.63 mmol) in ethyl acetate (20 mL) and ethanol (20 mL), was added conc.HCl (0.4 mL) and 10% Pd—C (100 mg) and the mixture hydrogenated in a Parr Shaker at 55 psi of hydrogen for 20 hrs. The reaction mixture was filtered through Celite, and the filtrate concentrated in vacuo to give an oil which was partitioned between ethyl acetate (10 mL) and water (10 mL). After separation, the aqueous phase was washed with additional ethyl acetate (5 mL). The combined extracts were concentrated in vacuo to dryness. The residual oil was triturated with ether to provide 145 mg (Yield 38%) of the title compound, as a tan powder: 1H NMR (CD3OD, 500 MHz) δ ppm: 3.06 (3H, s, NMe), 3.21 (3H, s, NMe), 4.11 (2H, s, NCH2), 7.13 (2H, m, Ar—Hs), 7.60 (1H, m, Ar—H); 13C NMR (CD3OD, 125.77 Hz) δ ppm: 36.03, 36.25 37.58, 110.79, 110.99, 113.26, 113.43, 122.32, 132.18, 132.25, 151.55, 154.72, 162.69, 164.67. HRMS (ESI) calcd for C10H13N2O2F (M+H) 213.1039, found 213.1039.

1. filtrationThe reaction mixture was filtered through Celite
2. concentrationthe filtrate concentrated in vacuo
3. customto give an oil which
4. customwas partitioned between ethyl acetate (10 mL) and water (10 mL)
5. customAfter separation
6. washthe aqueous phase was washed with additional ethyl acetate (5 mL)
7. concentrationThe combined extracts were concentrated in vacuo to dryness
8. customThe residual oil was triturated with ether