Diisopropylamine → 3-methyl-furan-2-carboxylic acid N'-[2-(5-fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetyl]-N'-isopropyl-hydrazide

HRID 2250927Notes

Reaction equation

HRID 2250927 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:20][C:21](O)=[O:22])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][C:15]([F:18])([F:17])[F:16])[CH:7]=1.[CH:24]([NH:27][NH:28][C:29]([C:31]1[O:32][CH:33]=[CH:34][C:35]=1[CH3:36])=[O:30])([CH3:26])[CH3:25].C(NC(C)C)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:20][C:21]([N:27]([CH:24]([CH3:26])[CH3:25])[NH:28][C:29]([C:31]2[O:32][CH:33]=[CH:34][C:35]=2[CH3:36])=[O:30])=[O:22])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][C:15]([F:18])([F:17])[F:16])[CH:7]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 2733179PyBroPHCID 58689904(5-Fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetic acidHCID 586899183-methyl-furan-2-carboxylic acid N'-isopropyl-hydrazide

Product 1

HCID 116846563-methyl-furan-2-carboxylic acid N'-[2-(5-fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetyl]-N'-isopropyl-hydrazideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (5-fluoro-2′-trifluoromethoxy-biphenyl-2-yloxy)-acetic acid (211 mg, 0.64 mmol) and 3-methyl-furan-2-carboxylic acid N′-isopropyl-hydrazide (140 mg, 0.768 mmol) in DMF (3 ml) was treated with diisopropyl amine (0.278 ml, 1.6 mmol) and PyBroP (448 mg, 0.96 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 50-100% ethyl acetate in hexanes gradient to afford the product as a white solid (180 mg, 57%). MS m/e 495.19 (M+H+)

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 50-100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-32845e93f4f7463f8081a94aded428bc
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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