Hydrochloric Acid → 3,4-Diethoxy-2-fluoro-6-methylbenzonitrile

HRID 2223757Notes

Reaction equation

HRID 2223757 reaction equation
C[Li].[CH3:3]C1(C)CCCC(C)(C)N1.[CH2:13]([O:15][C:16]1[C:17]([F:27])=[C:18]([CH:21]=[CH:22][C:23]=1[O:24][CH2:25][CH3:26])[C:19]#[N:20])[CH3:14].CI.Cl>O1CCCC1>[CH2:13]([O:15][C:16]1[C:17]([F:27])=[C:18]([C:21]([CH3:3])=[CH:22][C:23]=1[O:24][CH2:25][CH3:26])[C:19]#[N:20])[CH3:14]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 130352,2,6,6-TetramethylpiperidineHCID 230937173,4-Diethoxy-2-fluorobenzonitrileHCID 178418348HCID 178418348, compound

Product 1

HCID 230937073,4-Diethoxy-2-fluoro-6-methylbenzonitrileYield 81.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under a stream of nitrogen gas, methyl lithium (1.03 M diethyl ether solution, 18.2 mL, 18.8 mmol) was added to an ice-cooled solution of 2,2,6,6-tetramethylpiperidine (3.16 mL, 18.7 mmol) in tetrahydrofuran (30 mL), followed by 30 minutes of stirring. After cooling the reaction system to −78° C., a solution of 3,4-diethoxy-2-fluorobenzonitrile (3.90 g, 18.6 mmol) in tetrahydrofuran (20 mL) was added dropwise, and 30 minutes later, methyl iodide (1.4 mL, 22.4 mmol) was added dropwise, followed by 2 hours of stirring. The reaction system was gradually warmed to room temperature, and 1N hydrochloric acid was added to the reaction solution, after which ethyl acetate extraction was performed. The extract was washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off, and the residue was purified by silica gel column chromatography (n-hexane, ethyl acetate) to give 3.40 g of the subject compound (yield: 81.7%).

Workup

  1. waitfollowed by 2 hours
  2. stirringof stirring
  3. temperatureThe reaction system was gradually warmed to room temperature
  4. extractionafter which ethyl acetate extraction
  5. washThe extract was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtration
  8. distillationthe solvent was distilled off
  9. customthe residue was purified by silica gel column chromatography (n-hexane, ethyl acetate)

Sources & evidence

ORD record
ord-63ca4b2382d143e4b72d4bfe947d702e
Source dataset
uspto-grants-2008_05
Patent number
US07375236B2

Reaction notes

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