Water → 3,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamide

HRID 2181436Notes

Reaction equation

HRID 2181436 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20](I)=[CH:19][C:18]=2[F:24])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].C([O-])([O-])=O.[K+].[K+].O.N[C:33]1C=CC=C[CH:34]=1>C(COC)OC.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:33]([C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:3]2[C:2]([F:1])=[C:14]([F:15])[CH:13]=[CH:12][C:4]=2[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6])=[C:18]([F:24])[CH:19]=1)=[CH2:34]

Participants

8

Reactant 4

HCID 962Water2×HCID 6115AnilineHCID 11430Potassium CarbonateHCID 98038913,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)benzamide

Product 1

HCID 102369933,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamideYield 76%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (1.00 g, 2.21 mmol) was dissolved in dry dimethoxyethane (DME, 18 ml) under a nitrogen atmosphere, Pd(Ph3P)4 (0.13 g, 0.11 mmol) was added and the resulting yellow solution was stirred at ambient temperature for 20 min. K2CO3 (−325 mesh, 0.31 g, 2.21 mmol), water (5.3 ml) and boron complex 2 (0.54 g, 2.21 mmol) were added and the contents of the flask were refluxed for 1 h. 1 Water (50 ml) and brine (50 ml) were added and the aqueous phase was extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with brine (20 ml) and dried over MgSO4. The solvent was removed under vacuum and the residual dark orange oil was chromatographed (ethyl acetate as eluent) to give 0.59 g (76% yield) of 2-[(4-vinyl-2-fluorophenyl)amino]-3,4-difluoro-N-(2-hydroxy-ethoxy)benzamide as a light yellow solid, mp 134-137° C. 1H NMR (d6-DMSO) δ 3.53-3.54 (m, 2H), 3.82 (s, 2H), 4.69-4.72 (m, 1H), 5.14 (d, 1H, J=11 Hz), 5.69-5.77 (m, 1H), 6.57-6.64 (m, 1H), 6.77-6.83 (m, 1H), 7.09-7.18 (m, 2H), 7.33-7.40 (m, 2H), 8.74 (bs, 1H), 11.86 (bs, 1H).

Workup

  1. temperaturethe contents of the flask were refluxed for 1 h
  2. extractionthe aqueous phase was extracted with ethyl acetate (3×50 ml)
  3. washThe combined organic extracts were washed with brine (20 ml)
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed under vacuum
  6. customthe residual dark orange oil was chromatographed (ethyl acetate as eluent)

Sources & evidence

ORD record
ord-29a9a05280404bafaf26edf194f31689
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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