1-Benzoyl-2-isopropylhydrazine → benzoic acid N'-[2-(2-bromo-4,6-difluoro-phenoxy)-acetyl]-N'-isopropyl-hydrazide

HRID 2250895Notes

Reaction equation

HRID 2250895 reaction equation
[Br:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([F:14])[C:3]=1[O:4][CH2:5][C:6]([OH:8])=O.[CH:15]([NH:18][NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:17])[CH3:16].C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([F:14])[C:3]=1[O:4][CH2:5][C:6]([N:18]([CH:15]([CH3:17])[CH3:16])[NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:8]

Participants

6

Reactant 4

HCID 188691-Benzoyl-2-isopropylhydrazineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 58689913(2-Bromo-4,6-difluoro-phenoxy)-acetic acid

Product 1

HCID 58689916benzoic acid N'-[2-(2-bromo-4,6-difluoro-phenoxy)-acetyl]-N'-isopropyl-hydrazideYield 32.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2-bromo-4,6-difluoro-phenoxy)-acetic acid (0.92 g, 3.45 mmol) and benzoic acid N′-isopropyl-hydrazide (738 mg, 4.14 mmol) in DMF (20 ml) was treated with diisopropylethyl amine (1.5 ml, 8.625 mmol) and PyBroP (2.41 g, 5.175 mmol) at room temperature overnight. The reaction mixture was partitioned between 1N HCl and ethyl acetate. The organic layer was successively washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 20-30% ethyl acetate/hexanes gradient to afford the product as a white solid (478 mg, 1.12 mmol, 32%).

Workup

  1. customThe reaction mixture was partitioned between 1N HCl and ethyl acetate
  2. washThe organic layer was successively washed with saturated sodium bicarbonate and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was absorbed on silica
  7. custompurified on a silica gel column with a 20-30% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-8821214c46b040f4a43046f9a0d1a770
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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