Aniline → HCID 68685111, compound

HRID 1160787Notes

Reaction equation

HRID 1160787 reaction equation
[Cl:1][C:2]1[C:3]([F:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].NC1C=CC=CC=1.[CH2:17]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)[CH2:18][CH2:19][CH3:20].[F-].[Cs+]>O.[Pd].CN1CCCC1=O.O1CCOCC1>[ClH:1].[CH2:17]([C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:8]=[CH:7][CH:6]=[C:4]([NH2:5])[C:3]=2[F:9])=[CH:23][CH:22]=1)[CH2:18][CH2:19][CH3:20]

Participants

9

Reactant 4

HCID 6115AnilineHCID 25953Cesium fluorideHCID 750143-Chloro-2-fluoroanilineHCID 41008604-Butylphenylboronic acid

Product 1

HCID 68685111HCID 68685111, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of dioxane (16 mL) and N-methylpyrrolidinone (8 mL) is deoxygenated by passing a stream of nitrogen through it for 15 minutes. A sample of 3-chloro-2-fluoroaniline (3 g, 20.6 mmol) is charged to a 250 mL round-bottom flask which is equipped with a screw-top adapter capable of sealing the vessel via a 3 way stopcock. The aniline is then treated with 4-butylphenylboronic acid (5.5 g, 30.9 mmol), cesium fluoride (7.82 g, 51.5 mmol) and bis-(tri-tert-butyl phosphiono) palladium (527 mg, 1.03 mmol). The flask is evacuated, back filled with nitrogen, and sealed. The flask is placed into an oil bath which has been preheated to 130° C. and stirred for 4 hours. After cooling, the reaction is filtered through a pad of celite which is subsequently rinsed with EtOAc. The organics are then removed by rotary evaporation. The crude reaction is diluted with water, and extracted with EtOAc. The phases are separated, and the organics are dried over MgSO4, filtered, and concentrated. The resulting oil is diluted with diethyl ether and treated with an excess of a 4 M solution of HCl in dioxane. The resulting solid is collected, washed with diethyl ether, and dried to give 4′-butyl-2-fluoro-biphenyl-3-ylamine hydrochloride as a white solid: LC/MS calculated for [M+H]+ C16H19FN: 244.3, found: 244.2. A 0° C. mixture of 4′-butyl-2-fluoro-biphenyl-3-ylamine hydrochloride (5.4 g, 0.019 mol) in concentrated aqueous HCl (50 ml) is treated with the drop wise addition of sodium nitrite (1.3 g, 0.019 mol) in H2O (20 ml) over 10 minutes. The resulting solution is stirred at 0° C. for 1 hour and then treated with the drop wise addition of a 0° C. solution of tin (II) chloride (13.0 g, 0.058 mol) in concentrated aqueous HCl (14 ml). This mixture is stirred for 15 min and then filtered. The isolated solid is washed with cold saturated aqueous NaCl and then suspended in 50% NaOH. The resultant slurry is diluted with H2O and extracted with Et2O. The organic phase is dried over MgSO4, filtered, and concentrated. The resulting residue is dissolved in 100 ml of Et2O and cooled to 0° C. 4.0 M HCl in dioxane (15 ml) is added drop wise to this solution and the resulting precipitate collected to yield 4.58 g (81%) of the desired hydrazine hydrochloride. LC/MS calculated for C16H20FN2: 259.3 found: 259.2

Workup

  1. customis deoxygenated
  2. customfor 15 minutes
  3. customis equipped with a screw-top adapter capable
  4. customThe flask is evacuated
  5. additionback filled with nitrogen
  6. customsealed
  7. customThe flask is placed into an oil bath
  8. customhas been preheated to 130° C.
  9. temperatureAfter cooling
  10. filtrationthe reaction is filtered through a pad of celite which
  11. washis subsequently rinsed with EtOAc
  12. customThe organics are then removed by rotary evaporation
  13. customThe crude reaction
  14. extractionextracted with EtOAc
  15. customThe phases are separated
  16. dry with materialthe organics are dried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. additionThe resulting oil is diluted with diethyl ether
  20. additiontreated with an excess of a 4 M solution of HCl in dioxane
  21. customThe resulting solid is collected
  22. washwashed with diethyl ether
  23. customdried

Sources & evidence

ORD record
ord-88664b1a186544799d40bf4cb77e125a
Source dataset
uspto-grants-2010_10
Patent number
US07816542B2

Reaction notes

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