Sodium Hydroxide → 2,2-Bis-(4-fluoro-phenyl)-N-methyl-acetamide

HRID 392826Notes

Reaction equation

HRID 392826 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:9](O)=[O:10])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.Cl.[CH3:26][NH2:27].[OH-].[Na+]>ClCCl.O.O1CCCC1.C(OCC)(=O)C.CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:9]([NH:27][CH3:26])=[O:10])=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 6364545Methylamine hydrochlorideHCID 135116842,2-Bis(4-fluorophenyl)acetic acid

Product 1

HCID 226609732,2-Bis-(4-fluoro-phenyl)-N-methyl-acetamideYield 91.3%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of bis-(4-fluorophenyl)-acetic acid (8.07 g, 32.5 mmol) (prepared using the procedure of Takahashi, Y. et al., Chem. Lett., 1985, 1733.), in dichloromethane (30 ml) was treated at 22° C. with oxalyl chloride (5.5 ml, 65.0 mmol) and a drop of N,N-dimethylformamide. After 18 h at 22° C., the solvent and excess reagent were evaporated under reduce pressure. The residual oil was then dissolved in dry tetrahydrofuran (10 ml) and added dropwise and under good stirring to a cold (0-5° C.) mixture of methylamine hydrochloride (10.9 g, 0.16 mol), sodium hydroxide (6 g) in water (50 ml) and tetrahydrofuran (100 ml). After 1 h at 22° C., the reaction mixture was diluted with ethyl acetate, washed successively with water, 1N hydrochloric acid, saturated sodium bicarbonate, brine and dried (magnesium sulfate). Evaporation of the solvent and crystallization of the residue in ethyl acetate gave 7.75 g (91%) of the title material as white needles: mp 179-180° C. 1HNMR 400 MHz (CDCl3) δ (ppm): 2.86 (3H d, J=5.1 Hz, NCH3), 4.87 (1H, s, CH) 5.65 (1H, broad, NH), 7.04 and 7.23 (2×4H, 2 m, aromatics). Anal. Calcd for C15H13F2NO: C, 68.96; H, 5.02; N, 5.36. Found: C, 68.88; H, 4.49; N, 5.75.

Workup

  1. customprepared
  2. customthe solvent and excess reagent were evaporated
  3. dissolutionThe residual oil was then dissolved in dry tetrahydrofuran (10 ml)
  4. additionadded dropwise
  5. waitAfter 1 h at 22° C.
  6. washwashed successively with water, 1N hydrochloric acid, saturated sodium bicarbonate, brine
  7. dry with materialdried (magnesium sulfate)
  8. customEvaporation of the solvent and crystallization of the residue in ethyl acetate

Sources & evidence

ORD record
ord-bfbe3c79f5d74fb494214499fcc8f21d
Source dataset
uspto-grants-2004_10
Patent number
US06803378B2

Reaction notes

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