Carbonic Acid → 2-(((S)-1-(8-chloro-2-(2-fluoro-phenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid

HRID 216859Notes

Reaction equation

HRID 216859 reaction equation
Cl[C:2]1[C:11]([C@@H:12]([N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])[CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([Cl:25])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C(O)(O)=[O:37].C(#N)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>[Cl:25][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[N:3]=[C:2]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[F:26])[C:11]([C@@H:12]([NH:14][C:15]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=1[C:22]([OH:23])=[O:37])=[O:24])[CH3:13])=[CH:10]2

Participants

6

Reactant 4

HCID 767Carbonic AcidHCID 27343542-Fluorophenylboronic acidHCID 18373917Acetonitrile--water (1/1)HCID 57707774(S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Product 1

HCID 577077902-(((S)-1-(8-chloro-2-(2-fluoro-phenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

A mixture of (S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (0.5000 g, 1.347 mmol), 2-fluorobenzeneboronic acid (0.2073 g, 1.482 mmol), tetrakis(triphenylphosphine)palladium (0.07782 g, 0.06735 mmol), and sodium carbonate anhydrous (0.7138 g, 6.735 mmol) in acetonitrile-water (3:1) (12.00 mL, 1.346 mmol) was stirred at 85° C. After 28 h, the mixture was cooled to room temperature. The mixture was concentrated under reduced pressure to remove acetonitrile. The mixture was partitioned between CH2Cl2 (50 mL) and water (50 mL). The aqueous layer (pH 10˜11) was washed with CH2Cl2 (50 mL×2) to remove byproducts. The aqueous layer was treated with 2 N HCl (50 mL) and extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with water (50 mL×1), brine (50 mL×1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 2-(((S)-1-(8-chloro-2-(2-fluoro-phenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid as a solid: LC-MS (ESI) m/z 448.9 [M+H]+. The crude product was carried on crude without purification for the next step.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customto remove acetonitrile
  4. customThe mixture was partitioned between CH2Cl2 (50 mL) and water (50 mL)
  5. washThe aqueous layer (pH 10˜11) was washed with CH2Cl2 (50 mL×2)
  6. customto remove byproducts
  7. additionThe aqueous layer was treated with 2 N HCl (50 mL)
  8. extractionextracted with CH2Cl2 (50 mL×2)
  9. washThe combined organic layers were washed with water (50 mL×1), brine (50 mL×1)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-edd1f7e2b1f34b83a1b17b1891bbc41a
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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