Sulfuric Acid → 6-Aminomethyl-3,4-diethoxy-2-fluorobenzonitrile sulfate

HRID 732251Notes

Reaction equation

HRID 732251 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([F:17])=[C:6]([C:15]#[N:16])[C:7](=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:8]#[N:9])[CH3:2].[S:18](=[O:22])(=[O:21])([OH:20])[OH:19].COCCOC>[OH-].[Pd+2].[OH-].[C].C(N(CC)CC)C>[S:18]([OH:22])([OH:21])(=[O:20])=[O:19].[NH2:9][CH2:8][C:7]1[C:6]([C:15]#[N:16])=[C:5]([F:17])[C:4]([O:3][CH2:1][CH3:2])=[C:11]([O:12][CH2:13][CH3:14])[CH:10]=1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 80711,2-DimethoxyethaneHCID 229298414,5-Diethoxy-3-fluorophthalonitrile

Product 1

HCID 866230016-Aminomethyl-3,4-diethoxy-2-fluorobenzonitrile sulfateYield 76%

Reagents, catalysts & solvents 2

HCID 178502593HCID 178502593, compoundCatalystHCID 8471TriethylamineSolvent2×

Conditions

Temperature
-22 °C

Procedure

A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −22° C. under hydrogen atmosphere (atmospheric pressure) for 24 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL) and the combined filtrate was divided into five equal portions. After one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL) was added thereto, and the mixture was stirred. Then, triethylamine (0.56 mL, 4 mol) was added dropwise thereto and the mixture was stirred at room temperature for one hour. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.59 g of the ½ triethylamine solvate of the title compound (yield: 76%) as dark white crystals.

Workup

  1. filtrationAfter insoluble matter in the reaction mixture was filtered off
  2. washthe residue was washed with methanol (23 mL)
  3. concentrationAfter one of them was concentrated at room temperature under reduced pressure, 1,2-dimethoxyethane (9.2 mL)
  4. additionwas added
  5. stirringthe mixture was stirred
  6. stirringthe mixture was stirred at room temperature for one hour
  7. customPrecipitated crystals
  8. filtrationwere filtered
  9. washwashed with a 5% methanol-1,2-dimethoxyethane solution
  10. customdried at room temperature under reduced pressure

Sources & evidence

ORD record
ord-2f06102da0fb45d8831890ff6feb0c55
Source dataset
uspto-grants-2009_09
Patent number
US07585982B2

Reaction notes

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