Carbon Dioxide → 2-Fluoro-5-iodobenzoic acid

HRID 1168182Notes

Reaction equation

HRID 1168182 reaction equation
N(C(C)C)C(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([I:20])=[CH:16][CH:15]=1.[C:21](=[O:23])=[O:22].[OH-].[Na+]>C1COCC1.CCOC(C)=O.O.CCOCC>[F:13][C:14]1[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=1[C:21]([OH:23])=[O:22]

Participants

10

Reactant 5

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 96054-FluoroiodobenzeneHCID 14798Sodium HydroxideHCID 178418339Butyllithium

Product 1

HCID 27789252-Fluoro-5-iodobenzoic acidYield 58%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a −78° C. solution of iPr2NH (16.80 mL) in 200 mL freshly distilled THF is added n-butyllithium (68 mL) dropwise, maintaining the temperature of the reaction below −65° C. The reaction is stirred for 10 minutes, then 1-fluoro-4-iodobenzene (11.50 mL) as a solution in 10 mL THF is added over 20 minutes. The reaction is stirred at −78° C. or 90 minutes, then cannulated rapidly into diethyl ether (180 mL) and dry ice (approximately 75 g). The reaction is stirred at room temperature overnight. To the ether solution is added 1N NaOH (100 mL) and water (200 mL) and the solution placed in a separatory funnel. The aqueous layer is removed. The organic layer is washed with H2O (2×100 mL). All the aqueous portions are combined, chilled in ice/H2O, and acidified to pH 2 with 6N HCl. This solution is then extracted with diethyl ether (2×200 mL). The ether portions are combined, dried over Na2SO4, filtered, and concentrated to give a pale yellow solid. The solid is dissolved in a minimal amount of EtOAc on the steam bath, and hexanes are added to affect recrystallization. After standing in the freezer overnight, the product is obtained as a crystalline white solid (15.44 g, 58%). Physical characteristics are as follows: m.p. 157-159° C.; 1H NMR (300 MHz, CDCl3) δ8.34, 7.88, 6.97; IR (drift) 3098, 3079, 3051, 3017, 3007, 2998, 2981, 2971, 2881, 2817, 1708, 1681, 1300, 1236, 824 cm−1; Anal. Calcd for C7H4FIO2: C, 31.61; H, 1.52; Found: C, 31.70; H, 1.59.

Workup

  1. temperaturemaintaining
  2. customthe temperature of the reaction below −65° C
  3. stirringThe reaction is stirred at −78° C. or 90 minutes
  4. stirringThe reaction is stirred at room temperature overnight
  5. customthe solution placed in a separatory funnel
  6. customThe aqueous layer is removed
  7. washThe organic layer is washed with H2O (2×100 mL)
  8. temperaturechilled in ice/H2O
  9. extractionThis solution is then extracted with diethyl ether (2×200 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a pale yellow solid
  14. additionare added
  15. customrecrystallization
  16. customAfter standing in the freezer overnight

Sources & evidence

ORD record
ord-2ecc6c06c50040ac97cec4a4d798604f
Source dataset
uspto-grants-2003_09
Patent number
US06624160B2

Reaction notes

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