Ammonia → HCID 67352412, compound

HRID 1424786Notes

Reaction equation

HRID 1424786 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:11]=3[C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.[CH:22](Br)([CH3:24])[CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+].N>CN1CCCC1=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([O:21][CH:22]([CH3:24])[CH3:23])=[CH:17][C:11]=3[C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 63582-BromopropaneHCID 10796Cesium carbonateHCID 67352452HCID 67352452, compound

Product 1

HCID 67352412HCID 67352412, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 2-(4-fluorophenyl)-5-hydroxy-1-benzofuran-3-carboxylate (18.86 g, 65.9 mmol), isopropyl bromide (24.74 mL, 264 mmol) and cesium carbonate (42.9 g, 132 mmol) in dry N-Methyl-2-pyrrolidone (191 mL) was stirred at 60° C. under nitrogen for 20 hours. The resultant thick suspension was allowed to cool to room temperature and then 7% aqueous ammonia solution (200 mL) was added with rapid stirring. This mixture was extracted with heptane (700 mL) and then the aqueous phase was separated off. Ethyl acetate (˜100 mL) was added to the organic phase and the resultant mixture was shaken and then dried over Na2SO4 and evaporated to give a brown oil which crystallized on standing overnight. This material was recrystallized from hot methanol and the solid was collected by filtration, washed with methanol and finally dried under vacuum to give methyl 2-(4-fluorophenyl)-5-[(1-methylethyl)oxy]-1-benzofuran-3-carboxylate. LCMS (m/z, ES+)=329 (M+1). The mother liquors from the first recrystallization were crystallized a second time to give an additional batch of methyl 2-(4-fluorophenyl)-5-[(1-methylethyl)oxy]-1-benzofuran-3-carboxylate.

Workup

  1. temperatureto cool to room temperature
  2. extractionThis mixture was extracted with heptane (700 mL)
  3. customthe aqueous phase was separated off
  4. additionEthyl acetate (˜100 mL) was added to the organic phase
  5. stirringthe resultant mixture was shaken
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give a brown oil which
  9. customcrystallized
  10. waiton standing overnight
  11. customThis material was recrystallized from hot methanol
  12. filtrationthe solid was collected by filtration
  13. washwashed with methanol
  14. customfinally dried under vacuum

Sources & evidence

ORD record
ord-e9f2164a72504d5fb48a0574eeead633
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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