Acetic acid, 2-(triphenylphosphoranylidene)-, methyl ester → 3-(4-Fluoro-2-butylamino-phenyl)-acrylic acid methyl ester

HRID 1042500Notes

Reaction equation

HRID 1042500 reaction equation
CON(C)[C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[NH:12][CH2:13][CH2:14][CH2:15][CH3:16].[H-].[H-].[H-].[H-].[Li+].[Al+3].C1(P(=[CH:44][C:45]([O:47][CH3:48])=[O:46])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.C1(C)C=CC=CC=1>[CH3:48][O:47][C:45](=[O:46])[CH:44]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[NH:12][CH2:13][CH2:14][CH2:15][CH3:16]

Participants

6

Reactant 3

HCID 17453Acetic acid, 2-(triphenylphosphoranylidene)-, methyl esterHCID 21226445Aluminium lithium hydrideHCID 86649970HCID 86649970, compound

Product 1

HCID 668564993-(4-Fluoro-2-butylamino-phenyl)-acrylic acid methyl esterYield 30.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-35 °C

Procedure

To a solution of N-methoxy-N-methyl-4-fluoro-2-n-butylamino-benzamide (0.5 g, 1.97 mmol) in THF (8 mL) was added dropwise LiAlH4 (1 M in THF, 1.0 mL) at −45° C. The mixture was stirred for 40 minutes at −35° C. and then quenched by adding saturated aqueous KHSO4 solution. The mixture was diluted with EtOAc, washed with 3 N HCl, and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was reacted with methyl (triphenylphosphoranylidene)acetate (725 mg, 2.17 mmol) in toluene (4 mL) overnight at 100° C. The mixture was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (0.15 g, 30%) after purification by column chromatography (EtOAc:hexane=1:10).

Workup

  1. customquenched
  2. additionby adding saturated aqueous KHSO4 solution
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with 3 N HCl, and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washThe mixture was washed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c05f4fe73e97404981057567fe3fae32
Source dataset
uspto-grants-2013_10
Patent number
US08557872B2

Reaction notes

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