Dimethylformamide → HCID 86721102, compound

HRID 1396324Notes

Reaction equation

HRID 1396324 reaction equation
CC1(C)CCCC(C)(C)N1.[Li]CCCC.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[F:24].CN([CH:28]=[O:29])C>C1COCC1.O>[Cl:16][C:17]1[C:18]([F:24])=[C:19]([C:20]([CH3:23])=[CH:21][CH:22]=1)[CH:28]=[O:29]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 130352,2,6,6-TetramethylpiperidineHCID 27365904-Chloro-3-fluorotolueneHCID 178418339Butyllithium

Product 1

HCID 86721102HCID 86721102, compoundYield 7.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(Reference: E. J. Org. Chem. 2005, 2116-2123) To a solution of 2,2,6,6-tetramethylpiperidine (0.642 mL, 3.80 mmol) in THF (15 mL) at −78° C. was added n-BuLi (2.162 mL, 3.46 mmol) dropwise. The resulting solution was stirred at −78° C. for 1 h and added 1-chloro-2-fluoro-4-methylbenzene (0.5 g, 3.46 mmol) dropwise. The solution was stirred for additional 0.5 h and then added DMF (0.536 mL, 6.92 mmol). The reaction was stirred at −78° C. for 1.5 h and at ambient temperature for 12 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic layer was washed with brine and concentrated. The residue was purified by silica gel chromatography to yield the desired product (43 mg, 7%).

Workup

  1. stirringThe solution was stirred for additional 0.5 h
  2. stirringThe reaction was stirred at −78° C. for 1.5 h and at ambient temperature for 12 h
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organic layer was washed with brine
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7f417581a21441fbbceece8754427162
Source dataset
uspto-grants-2014_12
Patent number
US08901115B2

Reaction notes

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