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

HRID 1793006Notes

Reaction equation

HRID 1793006 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.[B].[CH2:33]([CH2:36]OC)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)=[CH2:36]

Participants

8

Reactant 5

HCID 962Water2×HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 5462311BoronHCID 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 2

HCID 178418397HCID 178418397, compoundCatalystHCID 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, 2 H), 3.82 (s, 2 H), 4.69–4.72 (m, 1 H), 5.14 (d, 1H, J=11 Hz), 5.69–5.77 (m, 1 H), 6.57–6.64 (m, 1 H), 6.77–6.83 (m, 1 H), 7.09–7.18 (m, 2 H), 7.33–7.40 (m, 2 H), 8.74 (bs, 1 H), 11.86 (bs, 1 H).

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-05e03083de6c4618867870fed822e0e5
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

Loading…