Carbon Dioxide → HCID 68703636, compound

HRID 2244373Notes

Reaction equation

HRID 2244373 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH3:14])=[CH:9][C:8]=1[F:15].CC([O-])(C)C.[K+].[C:22](=[O:24])=[O:23]>C1COCC1.O>[Cl:6][C:7]1[C:8]([F:15])=[C:9]([C:10]([NH:13][CH3:14])=[CH:11][CH:12]=1)[C:22]([OH:24])=[O:23]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 23665647Potassium tert-butoxideHCID 57495860HCID 57495860, compoundHCID 178418339Butyllithium

Product 1

HCID 68703636HCID 68703636, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-75 °C

Procedure

n-Butyllithium solution (1.6 M in hexane, 4.95 mL, 8.0 mmol) was added at −78° C. to THF (10 ml) under nitrogen. A solution of (4-chloro-3-fluoro-phenyl)-methyl-amine (575 mg, 4.0 mmol) in THF (3 mL) was added dropwise keeping the temperature below −70° C. The solution was stirred for 5 min at −75° C. Potassium tert-butylate (889 mg, 8 mmol) dissolved in THF (2 ml) was added within 15 min. The reaction was stirred at −75° C. for 2 h and treated with a large excess of dry ice. Within 30 min the reaction was warmed to RT. Water was added and the reaction was extracted twice with diethyl ether. The aqueous layer was acidified to pH1 with 1N aq. HCl solution and extracted twice with diethyl ether. The combined organic layers were washed with sat. aq. NaCl solution, dried over sodium sulfate, filtered and the solvent was removed in vacuo to yield 3-chloro-2-fluoro-6-methylamino-benzoic acid (83 mg, 11%). Light brown solid, 1HNMR (DMSO-d6, 300 MHz): δ 81 (s, 3H), 6.52 (d, J=9.2 Hz, 1H), 7.45 (t, J=9.1 Hz, 1H).

Workup

  1. customthe temperature below −70° C
  2. additionwas added within 15 min
  3. stirringThe reaction was stirred at −75° C. for 2 h
  4. temperatureWithin 30 min the reaction was warmed to RT
  5. extractionthe reaction was extracted twice with diethyl ether
  6. extractionextracted twice with diethyl ether
  7. washThe combined organic layers were washed with sat. aq. NaCl solution
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a69c14c20dff43bd9e3ea3ac26576d13
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

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