Dimethylformamide → HCID 86682264, compound

HRID 529701Notes

Reaction equation

HRID 529701 reaction equation
CC1(C)CCCC(C)(C)N1.[Li]CCCC.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:18]=1[CH3:27].CN([CH:31]=[O:32])C>C1COCC1>[Br:16][C:17]1[C:18]([CH3:27])=[CH:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][C:22]=1[CH:31]=[O:32]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 130352,2,6,6-TetramethylpiperidineHCID 227541411-Bromo-2-methyl-4-(trifluoromethyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 86682264HCID 86682264, compoundYield 48.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 100 mL round bottom flask were added 2,2,6,6-tetramethylpiperidine (2.8 mL, 16.6 mmol), and 50 mL THF. BuLi (9.5 mL, 15.2 mmol, 1.6 M hexane solution) was added via a syringe at 0° C. After stirring at 0° C. for 15 mins, ice bath was replaced with dry ice/ether bath. To another 25 mL round bottom flask was added 1-bromo-2-methyl-4-(trifluoromethyl)benzene (3.3 g, 13.8 mmol) and THF. After cooling with dry ice/acetone bath, this solution was cannular transferred to the first flask rapidly. Upon completion of transferring, DMF (2.1 mL, 27.6 mmol) was added immediately and the resulting reaction mixture was stirred at that temperature for 10 more minutes before it was allowed to warm to −20° C. slowly. The reaction was quenched at −20° C. with addition of 50 mL 1N HCl. This mixture was diluted with 100 mL water and extracted with 100 mL EtOAc/hexane 1:9. The organics were washed with 30 mL NaHCO3 aqueous solution, dried over sodium sulfate, filtered and concentrated. Crude product was purified by chromatography to give 1.8 g 2-bromo-3-methyl-5-(trifluoromethyl)benzaldehyde. 1H NMR (500 MHz, CDCl3) δ10.50 (s, 1H), 8.03 (d, J=1.4 Hz, 1H), 7.75 (d, J=1.5 Hz, 1H), 2.60 (s, 3H).

Workup

  1. customice bath was replaced with dry ice/ether bath
  2. temperatureAfter cooling with dry ice/acetone bath
  3. customthe resulting reaction mixture
  4. stirringwas stirred at that temperature for 10 more minutes before it
  5. temperatureto warm to −20° C. slowly
  6. customThe reaction was quenched at −20° C. with addition of 50 mL 1N HCl
  7. additionThis mixture was diluted with 100 mL water
  8. extractionextracted with 100 mL EtOAc/hexane 1:9
  9. washThe organics were washed with 30 mL NaHCO3 aqueous solution
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customCrude product was purified by chromatography

Sources & evidence

ORD record
ord-80f5fc9e49404598a39b223460002ab3
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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