Hydrochloric Acid → 4-[3,5-difluoro-4-(methylthio)-phenyl]-3-phenylfuran-2(5H)-one

HRID 1838499Notes

Reaction equation

HRID 1838499 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:12][C:13]([C:15]1[CH:20]=[C:19]([F:21])[C:18]([S:22][CH3:23])=[C:17]([F:24])[CH:16]=1)=O.C(N(C(C)C)CC)(C)C.N12CCCN=C1CCCCC2.Cl>C(#N)C>[F:24][C:17]1[CH:16]=[C:15]([C:13]2[CH2:12][O:9][C:8](=[O:10])[C:7]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:20]=[C:19]([F:21])[C:18]=1[S:22][CH3:23]

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 999Phenylacetic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 81531DiisopropylethylamineHCID 227458042-Bromo-1-[3,5-difluoro-4-(methylthio)-phenyl]ethanone

Product 1

HCID 227466594-[3,5-difluoro-4-(methylthio)-phenyl]-3-phenylfuran-2(5H)-oneYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a mixture of phenylacetic acid (4.2 g, 0.030 mol) and crude 2-bromo-1-[3,5-difluoro-4-(methylthio)-phenyl]ethanone (8.6 g, 0.030 mol) in anhydrous acetonitrile (100 mL) was added diisopropylethylamine (3.9 g, 0.030 mol). The reaction mixture was stirred for one hour at room temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (5.0 g, 0.032 mol) was added. After 2 hours the mixture was poured into dilute HCl and extracted with dichloromethane (1×200 mL, 2×75 mL). The combined extracts were dried using magnesium sulfate, and concentrated. The residue was treated with anhydrous acetonitrile (100 mL) and DBU (10.0 g, 0.065 mol), stirring at room temperature for 3 hours. The mixture was poured into dilute HCl and extracted with dichloromethane (1×200 mL, 2×50 mL). The combined extracts were dried using magnesium sulfate, and concentrated. Purification by silica gel chromatography using 5% dichloromethane/10% ethyl acetate in hexanes afforded 4-[3,5-difluoro-4-(methylthio)-phenyl]-3-phenylfuran-2(5H)-one as an orange liquid (7.2 g, 76%). 1H NMR (CDCl3/400 MHz) 7.37-7.41 (m, 5H), 6.97 (m, 2H 5.09 (s, 2H), 2.48 (s, 3H). ESHRMS m/z 319.0601 (M+H+, Calcd 319.0604). Anal. Calcd for C17H12F2O2S: C, 64.14; H, 3.80; Found: C, 63.56; H, 3.54.

Workup

  1. extractionextracted with dichloromethane (1×200 mL, 2×75 mL)
  2. customThe combined extracts were dried
  3. concentrationconcentrated
  4. stirringstirring at room temperature for 3 hours
  5. extractionextracted with dichloromethane (1×200 mL, 2×50 mL)
  6. customThe combined extracts were dried
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-eea370e0c9ec4dc685961080577610c8
Source dataset
uspto-grants-2004_01
Patent number
US06673818B2

Reaction notes

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