Diisopropylethylamine → 4-(2-methoxy-ethoxy)-benzoic acid N'-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N'-isopropyl-hydrazide

HRID 2250889Notes

Reaction equation

HRID 2250889 reaction equation
[Br:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=O.[CH:14]([NH:17][NH:18][C:19](=[O:31])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:22][CH:21]=1)([CH3:16])[CH3:15].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]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([N:17]([CH:14]([CH3:16])[CH3:15])[NH:18][C:19](=[O:31])[C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:24][CH:25]=1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3028732-(2-Bromo-4-fluorophenoxy)acetic acidHCID 2733179PyBroPHCID 596421644-(2-methoxy-ethoxy)-benzoic acid-N'-isopropyl hydrazide

Product 1

HCID 586899194-(2-methoxy-ethoxy)-benzoic acid N'-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N'-isopropyl-hydrazideYield 63.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2-bromo-4-fluoro-phenoxy)-acetic acid (164 mg, 0.66 mmol) and 4-(2-methoxy-ethoxy)-benzoic acid-N′-isopropyl hydrazide (200 mg, 0.79 mmol) in DMF (5 ml) was treated with diisopropylethyl amine (0.29 mL, 1.65 mmol) and PyBroP (462 mg, 0.99 mmol) at room temperature overnight. The reaction mixture was partitioned between 1N HCl and ethyl acetate. The organic layer was successively washed with water 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 45-60% ethyl acetate/hexanes gradient to afford the product as a solid (202 mg, 63%).

Workup

  1. customThe reaction mixture was partitioned between 1N HCl and ethyl acetate
  2. washThe organic layer was successively washed with water 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 45-60% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-d77f3b4af3c44d22929eb14cb3efef03
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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