Water → HCID 23003353, compound

HRID 396528Notes

Reaction equation

HRID 396528 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[CH3:11][O:12][C:13](=[O:34])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=2)[NH:17][C:16]=1[C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1.O>C(OCC)C.[Pd].C1COCC1.[Cl-].[Zn+2].[Cl-].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:11][O:12][C:13](=[O:34])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=2)[NH:17][C:16]=1[C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)=[CH:28][CH:27]=1

Participants

10

Reactant 4

HCID 962WaterHCID 9256ThiazoleHCID 23003358HCID 23003358, compoundHCID 178418339Butyllithium2×

Product 1

HCID 23003353HCID 23003353, compoundYield 72%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 3007855ZincchlorideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of thiazole (0.11 g, 1.23 mmol) in diethyl ether (4 ml) was added n-BuLi (1.55M in hexane, 0.79ml) at −78° C. under nitrogen atmosphere. After stirring for 30 min., zinc chloride (1.0M in diethyl ether, 3.7 ml, 3.7 mmol) was added, and the mixture stirred at 0° C. for 30 min. To the resulting mixture was added palladium catalyst prepared in THF (5 ml) by the treatment of a suspension of dichlorobis(triphenylphosphine)palladium(II) (0.22 g, 0.31 mmol) with n-BuLi (1.55M in hexane, 0.39 ml). Methyl[6-chloro-2-(4-bromobenzoyl)-1H-indol-3-yl]acetate (Example 206, 0.25 g, 0.61 mmol) was added to the mixture. The reaction mixture was heated at reflux temperature for 4 h., poured into water (50 ml), and extracted with ethyl acetate (50 ml). The combined extracts were washed with brine (50 ml), dried (MgSO4), and concentrated. This crude product was purified by flash column chromatography eluting with ethyl acetate-hexane (1:3) to afford 0.18 g (72%) of the title compound as yellow solids.

Workup

  1. stirringthe mixture stirred at 0° C. for 30 min
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux temperature for 4 h.
  4. extractionextracted with ethyl acetate (50 ml)
  5. washThe combined extracts were washed with brine (50 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThis crude product was purified by flash column chromatography
  9. washeluting with ethyl acetate-hexane (1:3)

Sources & evidence

ORD record
ord-18a910a227c94ea09b432b1438a5da55
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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