Triethylamine → 4-[2-(2,6-Difluorophenyl)-4,5-dihydro-4-oxazolyl]-N-(4-fluorophenyl)benzamide

HRID 964320Notes

Reaction equation

HRID 964320 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17](I)=[CH:16][CH:15]=2)[N:13]=1.[F:21][C:22]1[CH:28]=CC(N)=[CH:24][CH:23]=1.C1(P(C(P(C2C=CC=CC=2)C2C=CC=CC=2)(C)C)C2C=CC=CC=2)C=CC=CC=1.[C]=[O:59].C([N:62]([CH2:65]C)[CH2:63][CH3:64])C>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([C:65]([NH:62][C:63]3[CH:64]=[CH:28][C:22]([F:21])=[CH:23][CH:24]=3)=[O:59])=[CH:16][CH:15]=2)[N:13]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 97314-Fluoroaniline2×HCID 11058111Oxazole, 2-(2,6-difluorophenyl)-4,5-dihydro-4-(4-iodophenyl)-HCID 12091099Phosphine, (1-methylethylidene)bis[diphenyl-HCID 178418416HCID 178418416, compound

Product 1

HCID 190801254-[2-(2,6-Difluorophenyl)-4,5-dihydro-4-oxazolyl]-N-(4-fluorophenyl)benzamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

The compound of Example 2 (1.0 g, 3 mmol) and 4-fluoroaniline (0.33 g, 3 mmol) were dissolved in dimethylsulfoxide (20 mL) and treated with triethylamine (1 mL) and bis (diphenylphosphino) propane (0.1 g, 2 mmol). Carbon monoxide was bubbled through the mixture for 5 min and palladium acetate (0.05 g, 2 mmol) was added. The mixture was evacuated with carbon monoxide was released into the reaction by means of a balloon. The evacuation and carbon monoxide release was repeated and the reaction was heated to 70° C. under a carbon monoxide atmosphere for 6 h. The compound, 4-fluoroaniline (0.33 g. 3 mmol), was added and heating continued for 1 h. The mixture was allowed to stand overnight and was added to water (100 mL). The solid form was filtered, taken up in a mixture of dichloromethane and ethyl acetate, and dried over magnesium sulfate. The residue, after evaporation under reduced pressure, was subjected to chromatography on silica gel with hexanes/ethyl acetate (3:1 to 1:2) as eluent. The title compound (0.45 g) was a slightly orange solid: m.p. 210°-212° C. 1H NMR (DMSO-D6, 200 MHz) δ 10.4 (b s,NH), 8.0-7.2 (m,11H), 5.6 (m,1H), 4.8 (m,1H), 4.3 (m,1H).

Workup

  1. customCarbon monoxide was bubbled through the mixture for 5 min
  2. customThe mixture was evacuated with carbon monoxide
  3. customwas released into the reaction by means of a balloon
  4. temperatureheating
  5. waitto stand overnight
  6. filtrationThe solid form was filtered
  7. additiontaken up in a mixture of dichloromethane and ethyl acetate
  8. dry with materialdried over magnesium sulfate
  9. customThe residue, after evaporation under reduced pressure

Sources & evidence

ORD record
ord-33504ed5c9f6470cb39c1666b6422e5e
Source dataset
uspto-grants-1998_06
Patent number
US05767281

Reaction notes

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