Dichloromethane → HCID 15887218, compound

HRID 377217Notes

Reaction equation

HRID 377217 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])[CH:19]=2)[NH:14][C:13]=1I)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][C:31]=1B(O)O.[CH2:40](Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CO.C(OCC)(=O)C.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.Cl[Pd]Cl.[Fe+2]>[CH2:1]([O:8][CH2:9][C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])[CH:19]=2)[NH:14][C:13]=1[C:35]1[CH:30]=[C:31]([CH3:40])[CH:32]=[C:33]([CH3:36])[CH:34]=1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2734347(2,5-Dimethylphenyl)boronic acidHCID 15887217Methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate

Product 1

HCID 15887218HCID 15887218, compoundYield 1,999.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 21867641Toluene methanolSolvent

Conditions

Temperature
80 °C

Procedure

A vigorously stirred suspension of methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-iodo-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate (4.00 g, 8.12 mmol), 2,5-dimethylphenylboronic acid (1.83 g, 12.2 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.33 g, 0.406 mmol) in toluene/MeOH (5:2; 140 mL) was degassed via three vacuum/nitrogen ingress cycles and the resulting mixture was heated to approximately 80° C. 1 M Na2CO3 (20.3 mL, 20.3 mmol) was added dropwise via syringe and the resulting mixture maintained at reflux overnight. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtered through celite® washing copiously with ethyl acetate. The filtrate was poured into water and extracted with ethyl acetate (x3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent) to afford the title compound as a colourless foam (3.82 g, 100%).

Workup

  1. temperaturethe resulting mixture maintained
  2. temperatureat reflux overnight
  3. temperatureAfter cooling to ambient temperature
  4. filtrationfiltered through celite®
  5. washwashing copiously with ethyl acetate
  6. additionThe filtrate was poured into water
  7. extractionextracted with ethyl acetate (x3)
  8. extractionThe combined organic extract
  9. washwas washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-66ef0b6a335448aab50f51a63212a920
Source dataset
uspto-grants-2000_02
Patent number
US06025366

Reaction notes

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