Thionyl Chloride → N-(2,6-Difluoro-3-hydroxy-phenyl)-6-fluoro-3-(3-fluorophenyl)-2-methyl-benzamide

HRID 1771721Notes

Reaction equation

[F:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([CH3:11])[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[CH:4][CH:3]=1.O=S(Cl)Cl.[NH2:23][C:24]1[C:25]([F:32])=[C:26]([OH:31])[CH:27]=[CH:28][C:29]=1[F:30].C([O-])(O)=O.[Na+]>C1COCC1.O>[F:32][C:25]1[C:26]([OH:31])=[CH:27][CH:28]=[C:29]([F:30])[C:24]=1[NH:23][C:8](=[O:10])[C:7]1[C:2]([F:1])=[CH:3][CH:4]=[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:6]=1[CH3:11]

Participants

Conditions

Temperature: 80 °C

Procedure

To 6-fluoro-3-(3-fluorophenyl)-2-methyl-benzoic acid (3 g, 12.0 mmol, 1 eq) was added SOCl2 (60 mL) and the reaction heated at 80° C. overnight. The resulting mixture was concentrated in vacuo and the residue that remained dissolved in THF (20 mL) and added dropwise to a mixture of 3-amino-2,4-difluoro-phenol (1.93 g, 13.2 mmol, 1.1 eq) and NaHCO3 (2.32 g, 36.2 mmol, 3 eq) in THF (5 mL). After the addition, the reaction mixture was stirred at room temperature for 30 min. Water was added and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo to give the title compound (500 mg, 11%) which was used without further purification.

Workup

concentrationThe resulting mixture was concentrated in vacuo
dissolutionthe residue that remained dissolved in THF (20 mL)
additionAfter the addition
extractionthe aqueous layer was extracted with EtOAc
dry with materialThe combined organic extracts were dried (Na2SO4)
filtrationfiltered
customevaporated in vacuo

Sources & evidence

ORD record: ord-1de58e43f9dd4705bd064de36b8d4692
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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