Aniline, 4-chloro-2-fluoro-5-(phenylmethoxy)- → HCID 54260252, compound

HRID 862378Notes

Reaction equation

HRID 862378 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:5]([NH2:16])=[C:4]([F:17])[CH:3]=1.C[Al](C)C.[N:22]1([C:31]([O-])=[O:32])[CH:27]=[CH:26][CH:25]=[CH:24][N:23]1[C:28]([O-])=[O:29]>C1(C)C=CC=CC=1>[CH2:9]([O:8][C:7]1[C:2]([Cl:1])=[CH:3][C:4]([F:17])=[C:5]([N:16]2[C:28](=[O:29])[N:23]3[CH2:24][CH:25]=[CH:26][CH2:27][N:22]3[C:31]2=[O:32])[CH:6]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 183590Aniline, 4-chloro-2-fluoro-5-(phenylmethoxy)-HCID 16682925TrimethylaluminumHCID 19697335HCID 19697335, compound

Product 1

HCID 54260252HCID 54260252, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 4.8 g of 4-chloro-2-fluoro-5-(phenylmethoxy)benzenamine (19.1 mmol) in 30 mL of toluene was added 11.5 mL of a 2.0M solution of trimethylaluminum (23.0 mmol) in toluene at room temperature. The mixture was stirred at the same temperature for 10 min. Then, 5.22 g of diethyl 1,2,3,6-tetrahydro-, 1,2-pyridazinedicarboxylate (22.9 mmol) was added at room temperature. The mixture was warmed under reflux overnight. The mixture was then cooled to room temperature and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel, eluting with a 1:1 v:v mixture of ethyl acetate and n-hexane to give 6.20 g of the title product of Step A as a yellow solid melting at 165°-166° C. 1H NMR (CDCl3, 300 MHz) δ 4.2 (s, 4H), 5.1 (s, 2H), 6.0 (s, 2H), 7.0 (d, 1H), 7.4 (m, 6H).

Workup

  1. temperatureThe mixture was warmed
  2. temperatureunder reflux overnight
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography over silica gel
  5. washeluting with a 1:1 v
  6. additionv mixture of ethyl acetate and n-hexane

Sources & evidence

ORD record
ord-5ba0c7a7ceca45bcaae8c9f490c9aaac
Source dataset
uspto-grants-1998_02
Patent number
US05719104

Reaction notes

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