Hydrochloric Acid → 3-(2-Fluoro-4-methoxyphenyl)-3-oxopropanenitrile

HRID 1507465Notes

Reaction equation

HRID 1507465 reaction equation
[CH3:1][C:2]#[N:3].[Li]CCCC.[F:9][C:10]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:11]=1[C:12](Cl)=[O:13].[NH4+].[Cl-].Cl>O1CCCC1>[F:9][C:10]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:11]=1[C:12](=[O:13])[CH2:1][C:2]#[N:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 144847142-Fluoro-4-methoxybenzoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 534039523-(2-Fluoro-4-methoxyphenyl)-3-oxopropanenitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of MeCN (4.35 g, 106.0 mmol) in THF (200 mL) at −78° C. was added n-BuLi, 2.5 M in hexanes (32.5 mL, 79.5 mmol). The resulting solution was stirred for 20 minutes and then a solution of 2-fluoro-4-methoxybenzoyl chloride (5.00 g, 26.5 mmol) in tetrahydrofuran (THF) (50 mL) was added slowly. The reaction mixture was allowed to proceed for 1 hour at −78° C. and then saturated aqueous NH4Cl (250 mL) was added. As the reaction warmed to room temperature, it was acidified with 1 N HCl (250 mL). Then, the resulting mixture was extracted with 1:1 EtOAc:hexanes (500 mL), and the organic extract was washed with brine, dried over MgSO4, and evaporated in vacuo to provide 3.5 g (68% crude yield) of the title compound.

Workup

  1. waitto proceed for 1 hour at −78° C.
  2. extractionThen, the resulting mixture was extracted with 1:1 EtOAc
  3. extractionhexanes (500 mL), and the organic extract
  4. washwas washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-279b57e1f5724632be031ae043f8c2e2
Source dataset
uspto-grants-2015_12
Patent number
US09221814B2

Reaction notes

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