反応 #1994307

反応方程式

6-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester

6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester

sodium methoxide

→

6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester

収率 94.7%

溶媒

MeOH

反応条件

後処理

1. 1
   温度The suspension was cooled in an ice bath
2. 2
   その他the reaction was quenched with saturated aqueous NH4Cl solution (80 mL) and H2O (50 mL)
3. 3
   温度cooled in ice
4. 4
   ろ過The precipitate was filtered
5. 5
   洗浄washed with H2O
6. 6
   その他dried in air

実験手順

6-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester (15; 7.213 g, 0.0166 mol) was slurried in MeOH (80 mL). The suspension was cooled in an ice bath, and solid sodium methoxide (NaOMe; 1.08 g, 0.02 mol) was added. After 1 h, the reaction was quenched with saturated aqueous NH4Cl solution (80 mL) and H2O (50 mL) and then cooled in ice. The precipitate was filtered, washed with H2O followed by cold MeOH and dried in air to give 6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester (16; 4.93 g, 94%) as a white powder: mp 164.9-166.2° C.; 1H NMR (300 MHz, CDCl3) δ 7.20 (dd, JF-H=1.8 Hz, JH-H=8.7 Hz, 1H, aromatic), 7.10 (dd, JF-H=6.9 Hz, JH-H=8.7 Hz, 1H, aromatic), 5.84 (d, J=0.9 Hz, 1H, H3), 5.68 (br s, 1H, NH), 5.10 (t, J=9.3 Hz, 1H, H6), 3.98 (d, JF-H=1.5 Hz, 3H, OMe), 3.91 (s, 3H, CO2Me), 2.71 (d, J=9 Hz, 2H, H5); 13C{1H} NMR (75.4 MHz, CDCl3) δ 193.0 (C4), 163.6 (CO2Me), 153.8 (d, JF-C=251 Hz, C2′), 147.9 (C2), 144.6 (d, JF-C=13 Hz, C3′), 128.6 (d, JF-C=3 Hz, C1′/C4′), 126.8 (d, JF-C=11 Hz, C1′/C4′), 125.5 (d, JF-C=3 Hz, C5′), 121.5 (d, JF-C=4 Hz, C6′), 102.0 (C3), 61.6 (d, JF-C=5 Hz, OMe), 53.4, 50.8, 42.0; HRMS-ESI (m/z): calcd for C14H13ClFNO4, 313.0512. found, 313.0511. Anal. Calcd for C14H13ClFNO4: C, 53.60; H, 4.18; N, 4.46. Found: C, 53.30; H, 4.14; N, 4.35.

出典