Stannous Chloride → HCID 66904900, compound

HRID 1160788Notes

Reaction equation

HRID 1160788 reaction equation
Cl.[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[C:13]=2[F:19])=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].[N:20]([O-])=O.[Na+].[Sn](Cl)[Cl:25]>Cl.O>[ClH:25].[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([NH:18][NH2:20])[C:13]=2[F:19])=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5]

Participants

6

Reactant 3

HCID 24479Stannous ChlorideHCID 23668193Sodium NitriteHCID 68685111HCID 68685111, compound

Product 1

HCID 66904900HCID 66904900, compoundYield 81.8%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

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. stirringThis mixture is stirred for 15 min
  2. filtrationfiltered
  3. washThe isolated solid is washed with cold saturated aqueous NaCl
  4. additionThe resultant slurry is diluted with H2O
  5. extractionextracted with Et2O
  6. dry with materialThe organic phase is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe resulting residue is dissolved in 100 ml of Et2O
  10. temperaturecooled to 0° C
  11. addition4.0 M HCl in dioxane (15 ml) is added drop wise to this solution
  12. customthe resulting precipitate collected

Sources & evidence

ORD record
ord-7c13be3fcf794731a3c5f3ae8eafa272
Source dataset
uspto-grants-2010_10
Patent number
US07816542B2

Reaction notes

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