Hydrochloric Acid → 4-Chloro-2-(3-cyanobenzoyl)-5-methoxybenzoic acid

HRID 1428930Notes

Reaction equation

HRID 1428930 reaction equation
Br[C:2]1[CH:10]=[C:9]([Cl:11])[C:8]([O:12][CH3:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Li]CCCC.[C:19]([C:21]1[CH:22]=[C:23]([CH:30]=[CH:31][CH:32]=1)[C:24](N(OC)C)=[O:25])#[N:20].Cl>C1COCC1.O>[Cl:11][C:9]1[C:8]([O:12][CH3:13])=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([C:24](=[O:25])[C:23]2[CH:30]=[CH:31][CH:32]=[C:21]([C:19]#[N:20])[CH:22]=2)[CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 463186413-cyano-N-methoxy-N-methylbenzamideHCID 848076632-Bromo-4-chloro-5-methoxybenzoic acidHCID 178418339Butyllithium

Product 1

HCID 904182224-Chloro-2-(3-cyanobenzoyl)-5-methoxybenzoic acidYield 84.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of 2-bromo-4-chloro-5-methoxybenzoic acid (0.5 g, 1.88 mmol) in THF (15 mL) was treated with n-BuLi (1.6M in hexane) (1.7 ml, 2.82 mmol) and stirred for 1 h at −78° C. 3-Cyano-N-methoxy-N-methylbenzamide (0.35 g, 1.88 mmol) in THF (15 mL) was added dropwise and the reaction stirred for 1 h at −78° C., then overnight at rt. It was diluted with water (30 mL), acidified with 5N HCl (15 mL), and extracted with EtOAc (2×100 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated to obtain 4-chloro-2-(3-cyanobenzoyl)-5-methoxybenzoic acid (0.5 g, 84%) (316.33 [M−H]).

Workup

  1. stirringthe reaction stirred for 1 h at −78° C.
  2. customovernight
  3. customat rt
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1ba29539093940dd8c5e443cf7ef1616
Source dataset
uspto-grants-2015_01
Patent number
US08937178B2

Reaction notes

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