Hydrazine hydrate (1:1) → HCID 61734338, compound

HRID 1054306Notes

Reaction equation

HRID 1054306 reaction equation
O.[NH2:2][NH2:3].[C:4](#[N:8])/[CH:5]=[CH:6]/[CH3:7].[C:9]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][CH:10]=1.C(O[Na])(C)(C)C>C1COCC1.O>[C:9]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:10]=[CH:11][C:12]([CH2:15][N:2]2[C:4]([NH2:8])=[CH:5][C:6]([CH3:7])=[N:3]2)=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 24654Hydrazine hydrate (1:1)HCID 76689(1,1'-Biphenyl)-4-carboxaldehydeHCID 637921CrotononitrileHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 61734338HCID 61734338, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

(see, e.g., WO2009150614A1). To a solution of hydrazine monohydrate (hydrazine 78-82%) (0.51 ml, 10.5 mmol) in THF (2 mL), crotononitrile (mixture of cis and trans) (0.82 ml, 10.1 mmol) was added dropwise. The mixture was stirred at 40° C. for 2 h. The mixture was allowed to cool to room temperature and biphenyl-4-carboxaldehyde (1.82 g, 10.0 mmol) was added. The mixture was stirred at 40° C. for 2 h. The mixture was concentrated under reduced pressure. To the resulting yellow solid was added iPrOH (15 mL) and the suspension was transferred to a pressure vessel. t-BuONa (993 mg, 10.3 mmol) was added and the mixture was stirred at 100° C. for 2 h 30 min. The mixture was allowed to cool to room temperature and diluted with water (50 mL). The mixture was extracted with Et2O (50 mL×2). The combined organic layers were extracted with IN aq. HCl (2×30 mL). The combined aqueous phases were basified to pH 14 with 50% aq. NaOH and extracted with Et2O (50 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure to provide the title compound (885 mg, 34% over three steps) as a yellow solid. Crude was used in the next reaction without further purification. 1H NMR (500 MHz, DMSO-d6) δ 7.68-7.61 (m, 4H), 7.45 (t, J=7.5 Hz, 2H), 7.39 (d, J=7.9 Hz, 2H), 7.37-7.33 (m, 1H), 5.59 (s, 1H), 5.38 (s, 2H), 2.20 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ 151.46, 146.77, 140.52, 139.98, 134.32, 129.40, 128.62, 128.09, 127.51, 127.14, 91.23, 48.92, 11.54.

Workup

  1. temperatureto cool to room temperature
  2. stirringThe mixture was stirred at 40° C. for 2 h
  3. concentrationThe mixture was concentrated under reduced pressure
  4. additionTo the resulting yellow solid was added iPrOH (15 mL)
  5. customthe suspension was transferred to a pressure vessel
  6. stirringthe mixture was stirred at 100° C. for 2 h 30 min
  7. temperatureto cool to room temperature
  8. extractionThe mixture was extracted with Et2O (50 mL×2)
  9. extractionThe combined organic layers were extracted with IN aq. HCl (2×30 mL)
  10. extractionextracted with Et2O (50 mL×2)
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-554f4d8eec6146bcbf18fdfa0883d866
Source dataset
uspto-grants-2016_07
Patent number
US09394303B2

Reaction notes

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