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

HRID 1907126Notes

Reaction equation

HRID 1907126 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19][CH3:20])[C:13]=2[F:21])[CH2:8][C:9](=[O:11])[CH:10]=1)=[O:4].S(Cl)([Cl:25])(=O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([O:19][CH3:20])[C:13]=2[F:21])[CH2:8][C:9](=[O:11])[C:10]=1[Cl:25])=[O:4]

Participants

4

Reactant 2

HCID 24648Sulfuryl chlorideHCID 596121066-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester

Product 1

HCID 596121323-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl esterYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

6-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester (16; 483 mg, 1.54 mmol) was slurried in CH2Cl2 (10 mL) and cooled in an ice bath. A solution of SO2Cl2 (209 mg, 1.55 mmol) in CH2Cl2 (5 mL) was added dropwise. After 30 min, the reaction solution was quenched with 10% aqueous sodium bisulfite solution. The organic layer was separated, washed with saturated aqueous NaHCO3 solution, H2O and brine and then dried (MgSO4). The solution was evaporated to a yellow oil which was crystallized from cold methanol to give 3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester (33; 0.437 g, 81%) as a light yellow solid: mp 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 7.20 (dd, JF-H=1.5 Hz, JH-H=8.1 Hz, 1H, aromatic), 7.10 (dd, JF-H=6.9 Hz, JH-H=8.1 Hz, 1H, aromatic), 5.82 (br s, 1H, NH), 5.10 (t, J=9.3 Hz, 1H, H6), 3.98 (d, JF-H=1.5 Hz, 3H, OCH3), 3.97 (s, 3H, CO2CH3), 2.88 (d, J=9 Hz, 2H, H5); ESIMS m/z 347.9 ([M+H]+).

Workup

  1. temperaturecooled in an ice bath
  2. customthe reaction solution was quenched with 10% aqueous sodium bisulfite solution
  3. customThe organic layer was separated
  4. washwashed with saturated aqueous NaHCO3 solution, H2O and brine
  5. dry with materialdried (MgSO4)
  6. customThe solution was evaporated to a yellow oil which
  7. customwas crystallized from cold methanol

Sources & evidence

ORD record
ord-11719c7e83d24047bc46fd10cd294817
Source dataset
uspto-grants-2013_12
Patent number
US08598086B2

Reaction notes

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