反应详情

To a solution of DIEA (1.80 mL, 10.6 mmol) and 2-(3-amino-2-fluoro-6-nitrophenyl)ethanol (0.88 g, 4.40 mmol), as prepared in the preceding step, in THF (10 mL) in an ice-bath was added a solution of acetyl chloride (319 μL, 4.49 mmol) in THF (5 mL). After stirring for 1.5 hour, the ice-bath was removed and the mixture was continued to stir at ambient temperature overnight. Additional acetyl chloride (63 μL, 0.88 mmol) was added, and the mixture was stirred for another 16 hours. The solvents were removed, and the mixture was partitioned between DCM and H2O. The organic layer was separated, and the aqueous layer was back-extracted with DCM. The organic layers were combined, washed with H2O (twice), dried over Na2SO4, concentrated, and flash chromatographed on silica gel eluting with EtOAc/DCM (0, 1, 2, and 5%) to give the title compound (0.73 g, 69% yield) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ 7.85 (dd, J=9.0, 1.5 Hz, 1H), 6.68 (t, J=8.9 Hz, 1H), 4.38-4.35 (m, 4H), 3.38 (dt, J=6.6, 2.8 Hz, 2H), 2.03 (s, 3H).

1. customthe ice-bath was removed
2. stirringto stir at ambient temperature overnight
3. stirringthe mixture was stirred for another 16 hours
4. customThe solvents were removed
5. customthe mixture was partitioned between DCM and H2O
6. customThe organic layer was separated
7. extractionthe aqueous layer was back-extracted with DCM
8. washwashed with H2O (twice),
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customflash chromatographed on silica gel eluting with EtOAc/DCM (0, 1, 2, and 5%)