Hydrochloric Acid → Methyl 4-(2-(2,4-dihydroxyphenyl)-2-oxoethyl)-3-fluorobenzoate

HRID 410039Notes

Reaction equation

[C:1]([CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[F:14])#N.[C:15]1([CH:22]=[CH:21][CH:20]=[C:18]([OH:19])[CH:17]=1)[OH:16].Cl.C([O-])([O-])=[O:25].[Na+].[Na+]>B(F)(F)F.CCOCC.O>[OH:16][C:15]1[CH:17]=[C:18]([OH:19])[CH:20]=[CH:21][C:22]=1[C:1](=[O:25])[CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[F:14]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of methyl 4-(cyanomethyl)-3-fluorobenzoate (8 g, 41 mmol) and resorcinol (6.8 g, 62 mmol) in BF3-Et2O (100 ml) was bubbled with HCl at 0° C. for 15 min. The mixture was stirred at 75° C. for 16 hours. Then H2O (100 ml) was added and the solution was heated at 95° C. for 16 hours. The mixture was cooled to room temperature and neutralized by Na2CO3 and extracted with EtOAc (100 ml×3). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated to give the crude product. Purification by column chromatography (PE/EtOAc=10/1 to 3/1) gave Intermediate I as a white solid (6 g, 48%).

Workup

temperaturethe solution was heated at 95° C. for 16 hours
temperatureThe mixture was cooled to room temperature
extractionextracted with EtOAc (100 ml×3)
dry with materialdried with anhydrous Na2SO4
filtrationfiltered
customevaporated
customto give the crude product
customPurification by column chromatography (PE/EtOAc=10/1 to 3/1)

Sources & evidence

ORD record: ord-2090381fefcd42e393671d94fb5f563f
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759548B2

Reaction notes

Loading…