Sodium Carbonate → thiophene-3-carboxylic acid N'-[2-(5-fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetyl]-N'-isopropyl hydrazide

HRID 2250934Notes

Reaction equation

HRID 2250934 reaction equation
Br[C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][CH2:5][C:6]([N:8]([CH:17]([CH3:19])[CH3:18])[NH:9][C:10]([C:12]1[CH:16]=[CH:15][S:14][CH:13]=1)=[O:11])=[O:7].C([O-])([O-])=O.[Na+].[Na+].[F:31][C:32]([F:44])([F:43])[O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O>COCCOC>[F:24][C:22]1[CH:21]=[CH:20][C:3]([O:4][CH2:5][C:6]([N:8]([CH:17]([CH3:19])[CH3:18])[NH:9][C:10]([C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)=[O:11])=[O:7])=[C:2]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[O:33][C:32]([F:31])([F:44])[F:43])[CH:23]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 58689906Thiophene-3-carboxylic acid n'-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-n'-isopropyl-hydrazid

Product 1

HCID 11698918thiophene-3-carboxylic acid N'-[2-(5-fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetyl]-N'-isopropyl hydrazideYield 63.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of thiophene-3-carboxylic acid N′-[2-(2-bromo-4-fluoro-phenoxy)-acetyl]-N′-isopropyl-hydrazide (251 mg, 0.60 mmol) in DME (5 ml)/2M Na2CO3 (1.05 ml, 2.12 mmol) was with 2-trifluoromethoxyphenylboronic acid (187 mg, 0.91 mmol) and Pd[PPh3]4 (140 mg, 0.12 mmol) in a microwave oven at 150° C. for 10 min. The reaction mixture was partitioned between water and DCM. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was adsorbed on silica and purified on a silica gel column with a 30-50% ethyl acetate/hexane gradient to afford the product as a solid (188 mg, 63%). MS m/e 497.41 (M+H+)

Workup

  1. customThe reaction mixture was partitioned between water and DCM
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on a silica gel column with a 30-50% ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-09b65af868e14057a9f27678b678b667
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

Loading…