Triethylamine → HCID 22050221, compound

HRID 1831990Notes

Reaction equation

HRID 1831990 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:11]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[N:17]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:16](=[O:29])[C:15]=1[Br:30].C(N(CC)CC)C.C([O:46][CH2:47][C:48](Cl)=[O:49])(=O)C>C1COCC1.O>[Br:30][C:15]1[C:16](=[O:29])[N:17]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:18]([CH3:20])=[CH:19][C:14]=1[O:13][CH2:12][C:11]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:10]=1[CH2:9][NH:8][C:47](=[O:46])[CH2:48][OH:49]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 22050385HCID 22050385, compound

Product 1

HCID 22050221HCID 22050221, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3-bromo-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one trifluoroacetate (0.12 g, 0.00021 mol) in THF (2.0 mL) at 5° C., was added triethyl amine (0.036 g, 0.00035 mol) followed by the addition of acetoxyacetyl chloride (0.05 mL). The mixture was stirred at room temperature for 30 min, diluted with cold water (10 mL), and extracted the products with dichloromethane (2×10 mL). The combined organic extracts were washed with water, dried (Na2SO4) and concentrated to dryness. The residue was dissolved in ethanol (0.5 mL), added 1N NaoH (0.5 mL)and stirred at room temperature for 1 h. The resulting solution was diluted with water (15 mL), and extracted with dichloromethane (2×10 mL). The combined dichloromethane extracts were washed with water, dried (Na2SO4) and concentrated to dryness. The residue was purified by flash chromatography (1% MeOH in EtOAc) to afford the title compound (0.032 g, 30%) as a white amorphous powder: 1H NMR (CDCl3/400 Hz) δ 7.45 (m, 2H), 7.18 (m, 1H), 7.05 (m, 3H), 6.23 (s, 1H), 5.24 (s, 2H), 4.56 (d, 2H, J=6.4 Hz), 4.08 (d, 2H, J=5.2 Hz), 2.79 (t, 1H), and 2.08 (s, 3H;) 19F NMR (CDCl3/400 MHz) δ−111.88 (m), and −118.62 (m); ES-HRMS m/z 511.0482 (M+H C22H19N2O4F3Br requires 511.0475).

Workup

  1. extractionextracted the products with dichloromethane (2×10 mL)
  2. washThe combined organic extracts were washed with water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue was dissolved in ethanol (0.5 mL)
  6. additionadded 1N NaoH (0.5 mL)
  7. stirringstirred at room temperature for 1 h
  8. additionThe resulting solution was diluted with water (15 mL)
  9. extractionextracted with dichloromethane (2×10 mL)
  10. washThe combined dichloromethane extracts were washed with water
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated to dryness
  13. customThe residue was purified by flash chromatography (1% MeOH in EtOAc)

Sources & evidence

ORD record
ord-ca6654b1ec8840dbac1cb278801f9fae
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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