Oxalyl chloride → N-(6-acetyl-2-chloro-3-methoxyphenyl)-2-(trifluoromethyl)thiazole-4-carboxamide

HRID 925969Notes

Reaction equation

HRID 925969 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:18])([F:17])[C:9]1[S:10][CH:11]=[C:12]([C:14]([O-:16])=O)[N:13]=1.[Li+].[NH2:20][C:21]1[C:26]([Cl:27])=[C:25]([O:28][CH3:29])[CH:24]=[CH:23][C:22]=1[C:30](=[O:32])[CH3:31]>C(Cl)Cl.CN(C=O)C.O1CCOCC1>[C:30]([C:22]1[C:21]([NH:20][C:14]([C:12]2[N:13]=[C:9]([C:8]([F:7])([F:18])[F:17])[S:10][CH:11]=2)=[O:16])=[C:26]([Cl:27])[C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)(=[O:32])[CH3:31]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 299199881-(2-Amino-3-chloro-4-methoxyphenyl)ethanoneHCID 57816666Lithium 2-(trifluoromethyl)thiazole-4-carboxylate

Product 1

HCID 68792612N-(6-acetyl-2-chloro-3-methoxyphenyl)-2-(trifluoromethyl)thiazole-4-carboxamideYield 69%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (1.9 mL, 1.4 eq.) was added dropwise under nitrogen at 0° C. to a suspension of compound 252 (4 g, 1.2 eq.) in DCM (120 mL) and DMF (few drops). The reaction mixture was stirred at 0° C. for 30 min and then at room temperature for additional 3 hrs. The solid was removed by filtration under nitrogen and the filtrate was evaporated to give a yellow oil. This oil was solubilised in dioxane (30 mL) and added under nitrogen to a solution of 6-acetyl-2-chloro-3-methoxy aniline 201d (3.26 g, 1 eq.) in 1,4-dioxane (60 mL). The reaction mixture was stirred at room temperature for 3 days. The solvent was removed under reduced pressure, the residue was solubilised in dichloromethane, washed with water, dried over Na2SO4 and concentrated in vacuum. The crude oil was triturated in MeOH/Et2O mixture to give the compound 254a as a white solid in 69% yield. 1H NMR (CDCl3, 400 MHz): δ (ppm) 2.59 (s, 3H), 4 (s, 3H), 6.90 (d, J=8.75 Hz, 1H), 7.70 (d, J=8.75 Hz, 1H), 8.44 (s, 1H), 10.28 (s, 1H); 19F NMR (CDCl3, 376 MHz): δ (ppm) −61.08 (s, 3F).

Workup

  1. waitat room temperature for additional 3 hrs
  2. customThe solid was removed by filtration under nitrogen
  3. customthe filtrate was evaporated
  4. customto give a yellow oil
  5. stirringThe reaction mixture was stirred at room temperature for 3 days
  6. customThe solvent was removed under reduced pressure
  7. washwashed with water
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuum
  10. customThe crude oil was triturated in MeOH/Et2O mixture

Sources & evidence

ORD record
ord-570f8a2232f741f39ca3d11289ad6fba
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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