Hydrochloric Acid → 4-Biphenylacetic acid, 2'-fluoro-alpha-methyl-

HRID 1870838Notes

Reaction equation

HRID 1870838 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[CH:22][CH:21]=1.IC.Cl>O1CCCC1.CN(P(N(C)C)N(C)C)C.CCCCCC>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:1])[C:27]([OH:29])=[O:28])=[CH:22][CH:21]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 211014-Biphenylacetic acid, 2'-fluoro-HCID 178418339Butyllithium

Product 1

HCID 211064-Biphenylacetic acid, 2'-fluoro-alpha-methyl-

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 15355Hexamethylphosphorous triamideSolvent

Procedure

Diisopropylamine (16.4 ml) was dissolved in tetrahydrofuran (100 ml) and then a hexane solution (30.3 ml, 1.66 M) of n-butyllithium was added under ice-cooling, after which the resulting mixture was stirred for 15 minutes. Subsequently, thereto was added under ice-cooling a solution obtained by dissolving the above carboxylic acid (13.44 g) in tetrahydrofuran (100 ml), and thereafter, hexamethylphosphorus triamide (40 ml) was added, after which the resulting mixture was stirred under ice-cooling for one hour. Further, iodomethane (3.63 ml) was added and the resulting mixture was stirred for 3 hours. To the reaction mixture was added 10% hydrochloric acid (500 ml) and then the solution was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, then dried over sodium sulfate and thereafter concentrated under reduced pressure, to obtain 2-(2'-fluoro-biphenyl-4-yl)-propionic acid (16.64 g).

Workup

  1. temperaturecooling
  2. additionSubsequently, thereto was added under ice-
  3. temperaturecooling a solution
  4. customobtained
  5. stirringafter which the resulting mixture was stirred under ice-
  6. temperaturecooling for one hour
  7. stirringthe resulting mixture was stirred for 3 hours
  8. extractionthe solution was subjected to extraction with ethyl acetate
  9. washThe organic layer was washed with a saturated sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-efbb3aa291bd4b70a2f398298144ca32
Source dataset
uspto-grants-2000_08
Patent number
US06100260

Reaction notes

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