Hydrochloric Acid → HCID 22025610, compound

HRID 1793007Notes

Reaction equation

HRID 1793007 reaction equation
[F:1][C:2]1[C:3]([NH:13][C:14]2[CH:19]=[CH:18][C:17](I)=[CH:16][C:15]=2[F:21])=[C:4]([CH:9]=[CH:10][C:11]=1[F:12])[C:5]([O:7]C)=[O:6].O1CCOCC1.[CH2:28]([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH2:30].Cl>CCO.[OH-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:30]([C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:3]2[C:2]([F:1])=[C:11]([F:12])[CH:10]=[CH:9][C:4]=2[C:5]([OH:7])=[O:6])=[C:15]([F:21])[CH:16]=1)[CH:29]=[CH2:28]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 90628AllyltributylstannaneHCID 22025654HCID 22025654, compound

Product 1

HCID 22025610HCID 22025610, compoundYield 77.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

Methyl 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoate (1.00 g), 2.45 mmol) and (Ph3P)4Pd (568 mg, 0.49 mmol) were weighed into a dry flask which was fitted with a condensor and flushed with nitrogen. Dioxane (20 mL) and allyltributyltin (976 mg, 2.95 mmol) were added via syringe and the entire mixture heated at reflux overnight. All solvent was removed under reduced pressure and the residue loaded directly onto a silica gel column (10% EtOAc/PE as eluant). After chromatography, the crude methyl ester was obtained as a pale yellow oil which was dissolved in a mixture of EtOH (25 mL) and 1 M NaOH (25 mL) and stirred overnight at RT. The mixture was then diluted with water (70 mL) and acidified with 1 M HCl (approx. 30 mL), then extracted with EtOAc (3×100 mL). The combined EtOAc fractions were washed with water (100 mL), brine (100 mL), dried (Na2SO4), then the solvent removed under reduced pressure to afford a pale yellow solid which was purified by chromatography on silica gel (50% EtOAc/PE as eluant) to afford 2-(4-allyl-2-fluoroanilino)-3,4-difluorobenzoic acid as pale yellow needles (583 mg, 72%); m.p. (EtOAc/hexane) 199–201° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.68 (v br s, 1 H), 9.25 (br s, 1 H), 7.81 (ddd, J=8.3, 6.1, 2.0 Hz, 1 H), 7.07 (dd, J=12.2, 1.7 Hz, 1 H), 7.06–6.98 (m, 2 H), 6.93 (dd, J=8.2, 1.6 Hz, 1 H), 6.01–5.89 (m, 1 H), 5.13–5.03 (m, 2 H), 3.51–3.40 (m, 2H, obscured by H2O). Anal. calcd. for C16H12F3NO2: C, 62.5; H, 3.9; N, 4.6. Found C, 62.7; H, 4.1; N, 4.5.

Workup

  1. customwhich was fitted with a condensor
  2. customflushed with nitrogen
  3. temperaturethe entire mixture heated
  4. temperatureat reflux overnight
  5. customAll solvent was removed under reduced pressure
  6. customAfter chromatography, the crude methyl ester was obtained as a pale yellow oil which
  7. extractionextracted with EtOAc (3×100 mL)
  8. washThe combined EtOAc fractions were washed with water (100 mL), brine (100 mL)
  9. dry with materialdried (Na2SO4)
  10. customthe solvent removed under reduced pressure
  11. customto afford a pale yellow solid which
  12. customwas purified by chromatography on silica gel (50% EtOAc/PE as eluant)

Sources & evidence

ORD record
ord-2dc6b170e3ac4f2cbf2e0c712791378e
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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