4-Chloroaniline → HCID 86661475, compound

HRID 1942967Notes

Reaction equation

HRID 1942967 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[Li]CCCC.C1CCCCC1.[CH:20]1[CH:21]=[CH:22][C:23]([C:26]2[N:27]=[C:28]([Cl:33])[CH:29]=[C:30](Cl)[N:31]=2)=[CH:24][CH:25]=1>C1COCC1.C(Cl)(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:33][C:28]1[N:27]=[C:26]([C:23]2[CH:24]=[CH:25][CH:20]=[CH:21][CH:22]=2)[N:31]=[C:30]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:29]=1

Participants

8

Reactant 4

HCID 78124-ChloroanilineHCID 8078CyclohexaneHCID 77338FenclorimHCID 178418339Butyllithium

Product 1

HCID 86661475HCID 86661475, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 4-chloroaniline (127.6 mg, 1 mmol) in dry THF (2 mL) was cooled in a dry-ice/acetone bath and treated dropwise with a solution of nBuLi in cyclohexane (0.5 mL, 2M, 1 mmol). The mixture was treated with additional dry THF (2 mL) and was allowed to warm slightly (˜15 minutes) till the material went into solution. The material was then transferred by cannula into a solution of fenclorim (XXII) (225 mg, 1 mmol) and bis(triphenylphosphine)palladium(II) dichloride (35 mg, 0.05 mmol) in dry THF (2 mL). Rinsed with dry THF (2 mL) and stirred at room temperature for 30 minutes. The reaction was partitioned between saturated sodium bicarbonate and ethyl acetate. Added brine to help clear an emulsion. Separated layers and the aqueous layer was extracted twice with ethyl acetate. The combined organics was dried over magnesium sulfate, filtered and concentrated on a rotary evaporator to yield a film. The film was taken up in chloroform and loaded onto 100 g of silica gel. The silica gel was eluted with 10% ethyl acetate/hexanes followed by 20% ethyl acetate/hexanes. The appropriate fractions were concentrated to yield 6-chloro-N-(4-chlorophenyl)-2-phenylpyrimidin-4-amine (XXIII) as a film (161.87 mg). ESI/MS 315.9, 317.9 (M+H), 314.0, 316.0 (M−H).

Workup

  1. temperatureto warm slightly (˜15 minutes) till the material
  2. washRinsed with dry THF (2 mL)
  3. customThe reaction was partitioned between saturated sodium bicarbonate and ethyl acetate
  4. extractionSeparated layers and the aqueous layer was extracted twice with ethyl acetate
  5. dry with materialThe combined organics was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated on a rotary evaporator
  8. customto yield a film
  9. washThe silica gel was eluted with 10% ethyl acetate/hexanes
  10. concentrationThe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-78d0986aa9fe42e3941ef4711d748890
Source dataset
uspto-grants-2013_03
Patent number
US08389718B2

Reaction notes

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