Tetrahydrofuran → Ethyl 3-(7-methoxyquinolin-4-yl)propanoate

HRID 219068Notes

Reaction equation

HRID 219068 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[Br-].[CH2:33]([O:35][C:36](=[O:40])[CH2:37][CH2:38][Zn+])[CH3:34].C1COCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[OH-].[NH4+]>[CH3:13][O:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([CH2:38][CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:40])=[CH:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 106078294-Chloro-7-methoxyquinolineHCID 178471816HCID 178471816, compound

Product 1

HCID 67503802Ethyl 3-(7-methoxyquinolin-4-yl)propanoate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 14923Ammonium HydroxideSolvent

Procedure

4-chloro-7-methoxyquinoline (0.35 g, 2 mmol), tri-t-butylphosphonium tetrafluoroborate (0.05 g, 0.2 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.08 g, 0.09 mmol) were combined. The reaction vessel was purged and flushed with nitrogen three times, followed by addition of 3-ethoxy-3-oxopropylzinc bromide in THF (10 mL, 5 mmol, 0.5 M). The reaction mixture was microwaved at 150° C. for 60 minutes. Upon completion, ammonium hydroxide (10 mL) was added. After 30 minutes the mixture was filtered and the filtrate was partitioned between water and ethyl acetate. Extracted with ethyl acetate (3×20 mL). The organic layers were combined, washed with brine, dried over magnesium sulfate, and concentrated. Purified by MPLC with a gradient of 20 to 50% EtOAc in CH2Cl2. (ESI, pos. ion) m/z: 354.1 (M+H). Step 2.

Workup

  1. customThe reaction vessel was purged
  2. customflushed with nitrogen three times
  3. customThe reaction mixture was microwaved at 150° C. for 60 minutes
  4. filtrationAfter 30 minutes the mixture was filtered
  5. customthe filtrate was partitioned between water and ethyl acetate
  6. extractionExtracted with ethyl acetate (3×20 mL)
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customPurified by MPLC with a gradient of 20 to 50% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-5d532a41bc1f479f849ef0c3a60fb2b3
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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