Sodium Carbonate → benzoic acid N'-[2-(5,4'-difluoro-biphenyl-2-yloxy)-acetyl]-N'-isopropyl-hydrazide

HRID 2250897Notes

Reaction equation

HRID 2250897 reaction equation
Br[C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7].C([O-])([O-])=O.[Na+].[Na+].[F:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>COCCOC>[F:25][C:23]1[CH:22]=[CH:21][C:3]([O:4][CH2:5][C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[NH:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[C:2]([C:36]2[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 58689907benzoic acid N'-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N'-isopropyl-hydrazide

Product 1

HCID 11539098benzoic acid N'-[2-(5,4'-difluoro-biphenyl-2-yloxy)-acetyl]-N'-isopropyl-hydrazideYield 81.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of benzoic acid N′-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N′-isopropyl-hydrazide (50 mg, 0.122 mmol) in DME (3 ml)/2M Na2CO3 (215 uL, 0.427 mmol) was treated with 4-fluorobenzeneboronic acid (26 mg, 0.183 mmol) and Pd[PPh3]4 (28 mg, 0.0244 mmol) for 12 hours at 90° C. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 30-50% ethyl acetate/hexanes gradient to afford the product as a beige solid (42 mg, 81%). LC-MS m/e 425.28 (M+H+)

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. washThe organic layer was washed with 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 30-50% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-c10fa4da7fd4414794e65dba7baf2857
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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