Methanol → 6-methyl-pyrrolo[2,1-b]thiazole-7-carboxylic Acid Ethyl Ester

HRID 882788Notes

Reaction equation

HRID 882788 reaction equation
C[Zn]C.[CH2:4]([O:6][C:7]([C:9]1[C:10](Br)=[CH:11][N:12]2[CH:16]=[CH:15][S:14][C:13]=12)=[O:8])[CH3:5].CO.[CH3:20]C(OC)(C)C>C1(C)C=CC=CC=1.O1CCOCC1.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]>[CH2:4]([O:6][C:7]([C:9]1[C:10]([CH3:20])=[CH:11][N:12]2[CH:16]=[CH:15][S:14][C:13]=12)=[O:8])[CH3:5]

Participants

8

Reactant 4

HCID 887MethanolHCID 15413tert-Butyl methyl etherHCID 593168206-Bromo-pyrrolo[2,1-b]thiazole-7-carboxylic acid ethyl esterHCID 178477796HCID 178477796, compound

Product 1

HCID 593168376-methyl-pyrrolo[2,1-b]thiazole-7-carboxylic Acid Ethyl Ester

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

Under nitrogen atmosphere a solution of dimethylzinc in toluene (1.2 M, 19.1 mL) is added to a mixture of 6-bromo-pyrrolo[2,1-b]thiazole-7-carboxylic acid ethyl ester (11.4 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.23 mmol, complex with CH2Cl2) in dioxane (35 mL). The mixture is heated to reflux for 2 h, stirred at rt for 12 h and diluted by addition of MeOH (2.3 mL) and TBME. The mixture is washed with hydrochloric acid (1.0 M) and water, dried over MgSO4, concentrated in vacuo and purified by flash chromatography (gradient: heptane to heptane/EtOAc 8/2) to give the desired product. LC-MS: tR=0.91 min; [M+H]+=210.0.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 2 h
  3. washThe mixture is washed with hydrochloric acid (1.0 M) and water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (gradient: heptane to heptane/EtOAc 8/2)

Sources & evidence

ORD record
ord-eb14cc18bfec445bb3f173b5db2d66ae
Source dataset
uspto-grants-2012_08
Patent number
US08236801B2

Reaction notes

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