Sodium Methoxide → 6-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester

HRID 1907125Notes

Reaction equation

HRID 1907125 reaction equation
C1(OC([N:10]2[CH:15]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=3[F:25])[CH2:14][C:13](=[O:26])[CH:12]=[C:11]2[C:27]([O:29][CH3:30])=[O:28])=O)C=CC=CC=1.C[O-].[Na+]>CO>[CH3:30][O:29][C:27]([C:11]1[NH:10][CH:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=2[F:25])[CH2:14][C:13](=[O:26])[CH:12]=1)=[O:28]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 596121126-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-5,6-dihydro-4H-pyridine-1,2-dicarboxylic acid 2-methyl ester 1-phenyl ester

Product 1

HCID 596121066-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl esterYield 94.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.

Workup

  1. temperatureThe suspension was cooled in an ice bath
  2. customthe reaction was quenched with saturated aqueous NH4Cl solution (80 mL) and H2O (50 mL)
  3. temperaturecooled in ice
  4. filtrationThe precipitate was filtered
  5. washwashed with H2O
  6. customdried in air

Sources & evidence

ORD record
ord-67857c2e98a64a16bd973042b72c64e8
Source dataset
uspto-grants-2013_12
Patent number
US08598086B2

Reaction notes

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