Triethylamine → 6-Fluoro-7-methylisoquinolin-1(2H)-one

HRID 2370268Notes

Reaction equation

HRID 2370268 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[CH3:13])[CH:5]=[CH:6]C(O)=O.C([N:16]([CH2:19]C)CC)C.ClC(OCC)=[O:23].[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]2[C:10](=[CH:11][C:12]=1[CH3:13])[C:19](=[O:23])[NH:16][CH:6]=[CH:5]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 2774608261951-72-8

Product 1

HCID 592260506-Fluoro-7-methylisoquinolin-1(2H)-oneYield 41.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 10.0 g of 3-fluoro-4-methyl-cinnamic acid in 80 ml acetone were subsequently added at 0° C. 6.74 g triethylamine in 10 ml acetone followed by 7.83 g ethyl chloroformate. After stirring for 2 h at 0 to 5° C. a solution of 4.0 g sodium azide in 9.5 ml water was added. After stirring for 1 additional h the reaction mixture was poured onto 200 ml ice water and extracted twice with chloroform. The organic phase was dried over magnesium sulfate, 40 ml diphenylether were added and the chloroform was cautiously removed in vacuo. The residue was then added dropwise into 50 ml of diphenylether which had been preheated to 245° C. After complete addition it was stirred for 1 further h at 230-250° C. After cooling down to 150° C. the reaction mixture was poured into 270 ml heptane and after further cooling in an ice bath the precipitated product was filtered by suction and 4.1 g 6-fluoro-7-methyl-2H-isoquinolin-1-one (12) were obtained. Rt=1.25 min (Method B). Detected mass: 178.1 (M+H+).

Workup

  1. additionwas added
  2. extractionextracted twice with chloroform
  3. dry with materialThe organic phase was dried over magnesium sulfate, 40 ml diphenylether
  4. additionwere added
  5. customthe chloroform was cautiously removed in vacuo
  6. additionThe residue was then added dropwise into 50 ml of diphenylether which
  7. customhad been preheated to 245° C
  8. additionAfter complete addition it
  9. stirringwas stirred for 1 further h at 230-250° C
  10. additionwas poured into 270 ml heptane
  11. temperatureafter further cooling in an ice bath the precipitated product
  12. filtrationwas filtered by suction

Sources & evidence

ORD record
ord-c8142df9d1c344b6abcd4a5917c439e5
Source dataset
uspto-grants-2014_04
Patent number
US08710077B2

Reaction notes

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