N,N-二异丙基乙胺 → 7-氟-2H-3,1-苯并噁嗪-2,4-二酮

温度

0 °C

2-Amino-4-fluorobenzoic acid methyl ester. 2-Amino-4-fluorobenzoic acid (5.0 g, 32 mmol) was dissolved in DCM (50 mL) and cooled to 0° C. Hünig's base (11 ml, 64 mmol) was added followed by triphosgene (3.8 g, 13 mmol). The reaction mixture was stirred for 5 min then allowed to warm to ambient temperature over 45 min. Water was added to the mixture, which was then extracted with DCM (3×), and the combined organic layers were dried (MgSO4). Filtration and concentration provided 7-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione as a tan solid (3.94 g, 21.8 mmol, 68%), which was taken on directly to the next step. To a solution of 7-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (3.94 g, 21.8 mmol) in DMF (20 mL) was added dry methanol (8.8 mL, 220 mmol) and DMAP (0.27 g, 2.2 mmol). The mixture was allowed to stand overnight, and was then partitioned between EtOAc and water. The organic layer was washed with water (3×) and dried (MgSO4). Filtration and purification on silica gel (MPLC, hexanes/EtOAc) provided the title methyl ester as a white solid (1.89 g, 11.1 mmol, 51%). HPLC (reversed-phase): RT=8.66 min). 1H NMR (400 MHz, CDCl3): 7.87 (m, 1H), 6.37 (m, 2H), 3.86 (s, 3H).

1. temperatureto warm to ambient temperature over 45 min
2. extractionwas then extracted with DCM (3×)
3. dry with materialthe combined organic layers were dried (MgSO4)
4. filtrationFiltration and concentration

ORD记录

ord-a26ada851c2e40ae83c41cf3df0baf5b

来源数据集

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

专利号

US07241759B2