Potassium Carbonate → 2-(4'-Hydroxymethyl-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester

HRID 915757Notes

Reaction equation

HRID 915757 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH:5]([CH3:7])[CH3:6].[OH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.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>[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([C:25]2[CH:26]=[CH:27][C:22]([CH2:21][OH:20])=[CH:23][CH:24]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH:5]([CH3:7])[CH3:6]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 434038742-(4-Bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl ester

Product 1

HCID 671101672-(4'-Hydroxymethyl-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl esterYield 67%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Step 1B [Intermediate 2: 2-(4-Bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl ester (3.4 g, 9.71 mmol), 4-hydroxymethyl phenyl boronic acid (1.48 g, 9.71 mmol, 1 equiv.), Pd(PPh3)4 (561mg, 0.48 mmol, 0.05 equiv.) were dissolved in ethylene glycol dimethyl ether (90 mL) under N2 atmosphere and stirred at room temperature for 30 min. Then K2CO3 (2.68 g, 19.4 mmol, 2 equiv.) in H2O (30 mL) was introduced to the reaction mixture and heat to reflux overnight. After TLC confirmation of reaction completion, solvent was removed by rotovap, residue partitioned between EtOAc and brine, organic layer dried over MgSO4, solvent removed, crude residue was triturated with EtOAc to give 2-(4′-Hydroxymethyl-biphenyl-4-sulfonylamino)-3-methyl-butyric acid methyl ester in 67% yield (2.46 g).

Workup

  1. temperatureheat
  2. temperatureto reflux overnight
  3. customAfter TLC confirmation of reaction completion, solvent
  4. customwas removed by rotovap, residue
  5. custompartitioned between EtOAc and brine, organic layer
  6. dry with materialdried over MgSO4, solvent
  7. customremoved
  8. customcrude residue was triturated with EtOAc

Sources & evidence

ORD record
ord-8c703529e15b4b95b8196a302a61cbc9
Source dataset
uspto-grants-2007_09
Patent number
US07268135B2

Reaction notes

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