Potassium Carbonate → 2-[4'-(2,8-Bis-trifluoromethyl-quinolin-4-yloxymethyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid methyl ester

HRID 2075820Notes

Reaction equation

HRID 2075820 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:34]=[CH:33][C:12]([CH2:13][O:14][C:15]3[C:24]4[C:19](=[C:20]([C:25]([F:28])([F:27])[F:26])[CH:21]=[CH:22][CH:23]=4)[N:18]=[C:17]([C:29]([F:32])([F:31])[F:30])[CH:16]=3)=[CH:11][CH:10]=2)O1.[CH3:36][O:37][C:38](=[O:54])[CH:39]([NH:43][S:44]([C:47]1[CH:52]=[CH:51][C:50](Br)=[CH:49][CH:48]=1)(=[O:46])=[O:45])[CH:40]([CH3:42])[CH3:41].C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:36][O:37][C:38](=[O:54])[CH:39]([NH:43][S:44]([C:47]1[CH:48]=[CH:49][C:50]([C:9]2[CH:10]=[CH:11][C:12]([CH2:13][O:14][C:15]3[C:24]4[C:19](=[C:20]([C:25]([F:26])([F:28])[F:27])[CH:21]=[CH:22][CH:23]=4)[N:18]=[C:17]([C:29]([F:30])([F:31])[F:32])[CH:16]=3)=[CH:33][CH:34]=2)=[CH:51][CH:52]=1)(=[O:46])=[O:45])[CH:40]([CH3:42])[CH3:41]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 434038742-(4-Bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl esterHCID 865986314-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-2,8-bis-trifluoromethyl-quinoline

Product 1

HCID 865986322-[4'-(2,8-Bis-trifluoromethyl-quinolin-4-yloxymethyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid methyl esterYield 53.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Step 2B [Intermediate 5, G9591-162]: To 4-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-2,8-bis-trifluoromethyl-quinoline (1.5 g, 3.0 mmol, 1 equiv.) in 45 mL of ethylene glycol dimethyl ether was added 2-(4-Bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl ester (1.06 g, 3.0 mmol, 1.0 equiv.) and Pd(PPh3)4 (174 mg, 0.15 mmol, 0.05 equiv.) under N2. The reaction mixture was stirred for 0.5 hr, then an aqueous solution of K2CO3 (834 mg, 6.0 mmol, 2 equiv.) was added. The mixture was heat to reflux overnight. After cooling to room temperature, solvent was removed under vacuum. The residue was diluted with EtOAc (100 mL) and washed with brine solution. The organic layer was dried over anhydrous MgSO4, solvent evaporated under vacuum, and the crude product was purified on silica gel column (30% EtOAc/Hexane) to give 1.026 g of 2-[4′-(2,8-Bis-trifluoromethyl-quinolin-4-yloxymethyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid methyl ester in 53% yield.

Workup

  1. temperatureThe mixture was heat
  2. temperatureto reflux overnight
  3. customsolvent was removed under vacuum
  4. additionThe residue was diluted with EtOAc (100 mL)
  5. washwashed with brine solution
  6. dry with materialThe organic layer was dried over anhydrous MgSO4, solvent
  7. customevaporated under vacuum
  8. customthe crude product was purified on silica gel column (30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-f8fd16a995704ab1b768d73ffd140e24
Source dataset
uspto-grants-2011_04
Patent number
US07923446B2

Reaction notes

Loading…