Diisopropylethylamine → 5-(3-chloro-benzoylamino)-N-[2,6-dimethyl-4-(1,2,2,2-tetra-fluoro-1-trifluoromethyl-ethyl)-phenyl]-2-phenoxy-benzamide

HRID 1967647Notes

Reaction equation

HRID 1967647 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([CH:16]=1)[C:13](O)=[O:14])=[O:6].O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(C(C)C)CC)(C)C.[CH3:67][C:68]1[CH:74]=[C:73]([C:75]([F:84])([C:80]([F:83])([F:82])[F:81])[C:76]([F:79])([F:78])[F:77])[CH:72]=[C:71]([CH3:85])[C:69]=1[NH2:70]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([O:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[C:12]([CH:16]=1)[C:13]([NH:70][C:69]1[C:71]([CH3:85])=[CH:72][C:73]([C:75]([F:84])([C:76]([F:77])([F:78])[F:79])[C:80]([F:81])([F:82])[F:83])=[CH:74][C:68]=1[CH3:67])=[O:14])=[O:6]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 98824254-(1,1,1,2,3,3,3-Heptafluoropropan-2-yl)-2,6-dimethylanilineHCID 592023805-(3-Chloro-benzoylamino)-2-phenoxy-benzoic acid

Product 1

HCID 592023875-(3-chloro-benzoylamino)-N-[2,6-dimethyl-4-(1,2,2,2-tetra-fluoro-1-trifluoromethyl-ethyl)-phenyl]-2-phenoxy-benzamideYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(3-Chloro-benzoylamino)-2-phenoxy-benzoic acid (200 mg, 0.54 mmol) (see Example I2) was suspended in dichloromethane (2 ml), followed by the addition of bis(2-oxo-3-oxazolidinyl)phosphonic chloride “BOP-Cl” (208 mg, 0.81 mmol), diisopropyl-ethylamine “Hunigs base” (280 μl, 1.63 mmol) and 2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-aniline (158 mg, 0.54 mmol) (=4-heptafluoroisopropyl-2,6-dimethylaniline, prepared according to US 2002/198399). The reaction mixture was stirred for 18 hours at ambient temperature, followed by extraction with aqueous sodium bicarbonate (1N) and dichloromethane. The organic phase was washed successively with aqueous hydrochloric acid (2N) and aqueous sodium bicarbonate (1N), dried over sodium sulfate and concentrated. The residue was purified by preparative reverse phase chromatography to yield Compound No. A1 of Table A below (113 mg, 32% yield over three steps).

Workup

  1. extractionfollowed by extraction with aqueous sodium bicarbonate (1N) and dichloromethane
  2. washThe organic phase was washed successively with aqueous hydrochloric acid (2N) and aqueous sodium bicarbonate (1N)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by preparative reverse phase chromatography
  6. customto yield Compound No

Sources & evidence

ORD record
ord-a849e789c9464ef0b356702654d83e2a
Source dataset
uspto-grants-2013_04
Patent number
US08420855B2

Reaction notes

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