Nitrogen → Benzoic Acid

HRID 1019800Notes

Reaction equation

HRID 1019800 reaction equation
ClC1C([C@@H](N2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)C2=O)C)=CC2C(=CC(F)=CC=2)N=1.FC1C=C(B(O)[OH:34])C=CC=1.C(=O)([O-])[O-].[Na+].[Na+].N#N>CC#N.O.CCOC(C)=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>[C:22]([OH:23])(=[O:34])[C:21]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

9

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 57707970(S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 243Benzoic AcidYield 232.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-2-(1-(2-chloro-7-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione (150 mg, 423 μmol), 3-fluorophenylboronic acid (65 mg, 465 μmol) and sodium carbonate (90 mg, 846 μmol) in MeCN (8 mL) and water (2 mL) was purged with N2 followed by the addition of Pd(PPh3)4 (24 mg, 21 μmol) and the resulting mixture was stirred at 90° C. overnight. The reaction mixture was diluted with EtOAc washed with water, brine and dried over Na2SO4. Purification using preparatory TLC eluted with 100% EtOAc afforded 2-4(S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid (120 mg, 66%). Mass Spectrum (ESI) m/e=433 (M+1). 24(S)-1-(7-Fluoro-2-(3-fluorophenyl)-quinolin-3-yl)ethyl)carbamoyl)benzoic acid was dissolved in EtOH (2 mL) and cond HCl (0.1 mL) was added. The resulting solution was heated to 80° C. for 4 h. Solvent was removed and satd NaHCO3 was added to the reaction mixture and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated and purified via preparatory TLC using 3% MeOH/DCM saturated with NH3 gas to afford a white solid of 2-((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)isoindoline-1,3-dione (85 mg, 49%). Mass Spectrum (ESI) m/e=415 (M+1).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. customPurification
  4. washeluted with 100% EtOAc

Sources & evidence

ORD record
ord-7ad63195671f427e887755d08437e0e8
Source dataset
uspto-grants-2014_05
Patent number
US08716290B2

Reaction notes

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