Potassium Carbonate → 5',6'-Difluoro-biphenyl-2,3'-dicarboxylic acid 2-t-butyl ester

HRID 2361116Notes

Reaction equation

HRID 2361116 reaction equation
C[O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([F:11])=[C:6](Br)[CH:5]=1.[C:14]([O:18][C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B1OC(C)(C)C(C)(C)O1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+].[OH-].[Na+].[NH4+].[Cl-]>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.CCOC(C)=O.C1COCC1.CO.C1(C)C=CC=CC=1>[C:14]([O:18][C:19]([C:21]1[C:22]([C:6]2[C:7]([F:11])=[C:8]([F:10])[CH:9]=[C:4]([C:3]([OH:2])=[O:13])[CH:5]=2)=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

12

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 4376764Tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 58575897Methyl 3-bromo-4,5-difluorobenzoate

Product 1

HCID 710738195',6'-Difluoro-biphenyl-2,3'-dicarboxylic acid 2-t-butyl ester

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Bromo-4,5-difluoro-benzoic acid methyl ester (194 mg, 772 μmol, 1.0 eq.) was mixed with 2-t-butoxycarbonylphenylboronic acid pinacol ester (282 mg, 927 μmol, 1.2 eq.). Toluene (1.1 mL) was added followed by MeOH (409 μL), then K2CO3 (214 mg, 1.5 mmol, 2.0 eq.) predissolved in water (202 μL). The mixture was stirred, and the reaction vessel was capped, placed under vacuum and purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (89.2 mg, 77.2 μmol) was added. The vessel was recapped and microwaved at 110° C. for 50 minutes. The organic layer was removed and the product was evaporated under vacuum. THF (3 mL) and 1 M aqueous NaOH (1.5 mL, 2.0 eq.) was added and the mixture was stirred for 2 hours. EtOAc was added and mixture was acidified with saturated NH4Cl. The organic layers were extracted, dried and evaporated to yield 5′,6′-difluoro-biphenyl-2,3′-dicarboxylic acid 2-t-butyl ester.

Workup

  1. customthe reaction vessel was capped
  2. custompurged with nitrogen
  3. custommicrowaved at 110° C. for 50 minutes
  4. customThe organic layer was removed
  5. customthe product was evaporated under vacuum
  6. stirringthe mixture was stirred for 2 hours
  7. extractionThe organic layers were extracted
  8. customdried
  9. customevaporated

Sources & evidence

ORD record
ord-39d62be587a443c6aea4b5afe74c0ef5
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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