Stannous chloride dihydrate → 5'-Amino-3,2'-difluorobiphenyl-2-carbonitrile

HRID 2183961Notes

Reaction equation

HRID 2183961 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH:13]=[C:12]([N+:14]([O-])=O)[CH:11]=[CH:10][C:9]=2[F:17])[C:3]=1[C:18]#[N:19].O.O.[Sn](Cl)Cl>O1CCCC1.C(O)C>[NH2:14][C:12]1[CH:11]=[CH:10][C:9]([F:17])=[C:8]([C:4]2[C:3]([C:18]#[N:19])=[C:2]([F:1])[CH:7]=[CH:6][CH:5]=2)[CH:13]=1

Participants

5

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 222852823,2'-Difluoro-5'-nitrobiphenyl-2-carbonitrile

Product 1

HCID 222852945'-Amino-3,2'-difluorobiphenyl-2-carbonitrileYield 100%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-bromo-6-fluorobenzonitrile (2.50 g, 12.5 mmol), potassium fluoride (2.40 g, 41.3 mmol) and 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (4.67 g, 17.5 mmol) in tetrahydrofuran (50 ml) was degassed with nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphine (0.2M solution in 1,4-dioxane, 3.7 ml) were added and the mixture stirred at ambient temperature for 15 min then at 50° C. for 18 h. After cooling to ambient temperature, the resulting dark suspension was poured onto 0.5M sodium hydroxide solution (500 ml) and stirred vigorously for 2 h. The dark solid was collected by filtration, washed with water (100 ml) and isohexane (50 ml) and left to air dry which gave 3,2′-difluoro-5′-nitrobiphenyl-2-carbonitrile as a brown/black solid (3.25 g, 100%): δH (360 MHz, CDCl3) 7.32-7.44 (3H, m), 7.71-7.77 (1H, m), 8.35-8.41 (2H, m). 3,2′-Difluoro-5′-nitrobiphenyl-2-carbonitrile (3.25 g, 12.5 mmol) in tetrahydrofuran (20 ml) and ethanol (20 ml) was treated with tin(II) chloride dihydrate (9.86 g, 43.8 mmol) and the mixture left to stir at ambient temperature for 18 h. The solvent was evaporated and the residue stirred with 2N sodium hydroxide solution (40 ml) for 2 h. The resulting suspension was diluted with water (100 ml) and extracted with dichloromethane (3×200 ml). The combined organics were washed with water (200 ml), brine (200 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give 5′-amino-3,2′-difluorobiphenyl-2-carbonitrile as a brown solid (2.87 g, 100%): δH (360 MHz, CDCl3) 3.74 (2H, s), 6.66-6.75 (2H, m), 7.01 (1H, dd, J 9 and 9), 7.19-7.30 (2H, m), 7.59-7.65 (1H, m).

Workup

  1. waitthe mixture left
  2. customThe solvent was evaporated
  3. stirringthe residue stirred with 2N sodium hydroxide solution (40 ml) for 2 h
  4. additionThe resulting suspension was diluted with water (100 ml)
  5. extractionextracted with dichloromethane (3×200 ml)
  6. washThe combined organics were washed with water (200 ml), brine (200 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-42450ac77ea241d9ba48482c7c718199
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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