3-Chloroaniline → HCID 67163917, compound

HRID 552490Notes

Reaction equation

HRID 552490 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C[Al](C)C.C([O:15][C:16]([C:18]1[CH:23]=[C:22]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH:21]=[C:20]([CH3:31])[N:19]=1)=O)C>O1CCOCC1.CCCCCC>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:16]([C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH:21]=[C:20]([CH3:31])[N:19]=2)=[O:15])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 79323-ChloroanilineHCID 16682925TrimethylaluminumHCID 67165343HCID 67165343, compound

Product 1

HCID 67163917HCID 67163917, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 113 μl (138 mg, 1.08 mmol, 4.0 equiv.) of 3-Chloroaniline in 7 ml of dry dioxane were added 540 μl (1.08 mmol, 4.0 equiv.) of a 2M solution of trimethylaluminium in hexane. The solution was stirred for 45 min at room temperature. Then a solution of 70.0 mg (0.27 mmol) of 4-(4-Fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid ethyl ester in 1 ml of dry dioxane was added and the reaction was heated to 100° C. for 1 h. The reaction was quenched by cautious addition of 0.7 ml of water. Then approximately 1 g of anhydrous sodium sulfate were added to bind the water and the mixture was stirred vigorously for 5 min. The mixture was diluted by addition of 10 ml of methylenene chloride and filtered over Speedex filter aid which was washed with methylene chloride. The filtrate was concentrated in vaccuo and the residue (248 mg orange solid) was purified by flash chromatography (heptane/ethyl acetate 4:1) to yield the title compound (68.0 mg, 74%) as a crystalline white solid, MS (ISP): m/e=341.0, 343.0 (M+H)+.

Workup

  1. temperaturethe reaction was heated to 100° C. for 1 h
  2. customThe reaction was quenched by cautious addition of 0.7 ml of water
  3. additionThen approximately 1 g of anhydrous sodium sulfate were added to bind the water
  4. stirringthe mixture was stirred vigorously for 5 min
  5. additionThe mixture was diluted by addition of 10 ml of methylenene chloride
  6. filtrationfiltered over Speedex
  7. filtrationfilter aid which
  8. washwas washed with methylene chloride
  9. concentrationThe filtrate was concentrated in vaccuo
  10. customthe residue (248 mg orange solid) was purified by flash chromatography (heptane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-fbc5fb44f4054bdcbc6fbc98f0199fac
Source dataset
uspto-grants-2011_05
Patent number
US07951824B2

Reaction notes

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