4'-Cyanoacetophenone → HCID 86638943, compound

HRID 244389Notes

Reaction equation

HRID 244389 reaction equation
[CH2:1]([C:4]1[CH:9]=[N:8][CH:7]=[CH:6][N:5]=1)[CH2:2][CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:20]([C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1)(=O)[CH3:21].C(=O)(O)[O-:32].[Na+]>O1CCCC1>[CH2:2]([C:1]1[C:4]2[C:9](=[N:8][CH:7]=[CH:6][N:5]=2)[NH:28][C:27]=1[C:26]1[CH:29]=[CH:30][C:23]([CH2:20][CH:21]=[O:32])=[CH:24][CH:25]=1)[CH3:3]

Participants

6

Reactant 4

HCID 740444'-Cyanoacetophenone2×HCID 87466Propylpyrazine2×HCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 86638943HCID 86638943, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-propylpyrazine (compound 2, 912 mg, 7.46 mmol) in tetrahydrofuran (5 mL) was added drop-wise, over a period of seven minutes, to a solution of sodium bis(trimethylsilyl)amide (2M solution in THF; 13 mL, 26 mmol, 3.5 equiv) at 20° C. A deep, purple-red solution was obtained and the temperature fell to 16.4° C. A solution of 4-acetylbenzonitrile (compound 3, 1.08 g, 7.4 mmol) in tetrahydrofuran (5 mL) was added, over a period of 18 minutes, at 13.3° C. The temperature fell to 12.6° C. and a brown solution ensued. The mixture was stirred at room temperature for one hour, heated to about 35° C. for six hours, then left to stir at room temperature for about 60 hours. The mixture was poured into aqueous saturated sodium bicarbonate (200 mL) and extracted with ethyl acetate (2×150 mL). The ethyl acetate was washed with water (100 mL) and concentrated on the Buchi at a bath temperature of 40° C. and from 80 to 10 torr to give a deep-yellow solid. The solid was triturated with diethyl ether (25 mL), filtered and washed with ether (25 mL). The solid was air dried to give 600 mg (30.3%) of compound 4 as a yellow solid: 1H NMR (300 MHz, CDCl3, FIG. 1) δ 8.5 (1H, d, J=2 Hz), 8.15 (2H, d, J=8 Hz), 8.1 (1H, d, J=3 Hz), 7.9 (2H, d, J=8 Hz), 3.1 (2H, q, J=9 Hz), 2.7 (3H, s), 1.4 (3H, t, J=9 Hz).

Workup

  1. customat 20° C
  2. customA deep, purple-red solution was obtained
  3. customfell to 16.4° C
  4. customfell to 12.6° C.
  5. temperatureheated to about 35° C. for six hours
  6. waitleft
  7. stirringto stir at room temperature for about 60 hours
  8. extractionextracted with ethyl acetate (2×150 mL)
  9. washThe ethyl acetate was washed with water (100 mL)
  10. concentrationconcentrated on the Buchi at a bath temperature of 40° C.
  11. customfrom 80 to 10 torr to give a deep-yellow solid
  12. customThe solid was triturated with diethyl ether (25 mL)
  13. filtrationfiltered
  14. washwashed with ether (25 mL)
  15. customdried

Sources & evidence

ORD record
ord-6e0eb5c15b5642e68eca665a34e35df8
Source dataset
uspto-grants-2014_02
Patent number
US08658649B2

Reaction notes

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