Potassium Carbonate → 5-{5-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-pyridin-2-yl}-pentanoic acid ethyl ester

HRID 2120678Notes

Reaction equation

HRID 2120678 reaction equation
[CH2:1]([N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15])[CH2:2][CH:3]=[CH2:4].B1C2CCCC1CCC2.C([O-])([O-])=O.[K+].[K+].[CH2:31]([O:33][C:34](=[O:46])[CH2:35][CH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42](Br)=[CH:41][N:40]=1)[CH3:32]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:31]([O:33][C:34](=[O:46])[CH2:35][CH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:4][CH2:3][CH2:2][CH2:1][N:5]2[C:13](=[O:14])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:15])=[CH:41][N:40]=1)[CH3:32]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 339432N-(3-Buten-1-yl)phthalimideHCID 235812715-(5-Bromo-pyridin-2-yl)-pentanoic acid ethyl ester

Product 1

HCID 235812725-{5-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-pyridin-2-yl}-pentanoic acid ethyl ester

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 8-5 (4.23 g, 21 mmol) in degassed THF (20 mL) at 0° C. was added dropwise a solution of 9-BBN (50.4 mL of 0.5 M in TBF, 25.2 mmol) and the mixture stirred for 18 hours at ambient temperature. K2CO3 (5.0 g, 35.8 mmol) and 8-2 (5.0 g, 17.4 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (0.54 g, 2.4 mmol) and DPPF (1.45 g, 2.6 mmol) in degassed DMF (20 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. To the stirring residue dissolved in THF (200 mL) was added water (75 mL) and NaHCO3 (16.5 g) and after 10 minutes, NaBO3.H2O (24 g). After vigorous stirring for 30 minutes, the mixture was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated to an oil. The residue was chromatographed on silica gel (20-40% EtOAc/hexane) to give 8-6 as a yellow solid.

Workup

  1. additiona premixed
  2. stirringThe resulting mixture was stirred for 18 hours at 70° C.
  3. temperaturecooled
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. dissolutionTo the stirring residue dissolved in THF (200 mL)
  8. additionwas added water (75 mL) and NaHCO3 (16.5 g)
  9. waitafter 10 minutes
  10. stirringAfter vigorous stirring for 30 minutes
  11. additionthe mixture was diluted with ethyl acetate
  12. washwashed with water and brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated to an oil
  15. customThe residue was chromatographed on silica gel (20-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-79b28ea8d62f46358d7ab7ed8f45ee46
Source dataset
uspto-grants-2004_02
Patent number
US06693101B2

Reaction notes

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