Dimethylformamide → 1-[5-(3-Chloro-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 1039993Notes

Reaction equation

HRID 1039993 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.CC(O)(C(C)(O)C)C.Br[C:29]1[S:33][C:32]([C:34]2([OH:38])[CH2:37][CH2:36][CH2:35]2)=[N:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:29]2[S:33][C:32]([C:34]3([OH:38])[CH2:37][CH2:36][CH2:35]3)=[N:31][CH:30]=2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 58456224HCID 58456224, compoundHCID 674337372,3-Dimethylbutane-2,3-diol 2-(3-chloro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 674321141-[5-(3-Chloro-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanolYield 54.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Step 1 (1.6 g, 3.98 mmol), Intermediate 1 (839 mg, 3.58 mmol), PdCl2 (dppf)-dichloromethane adduct (163 mg, 0.199 mmol), sodium carbonate (2M in water) (5.97 mL, 11.95 mmol), and DMF (39.8 mL) were heated at 100° C. for 2 hours under nitrogen. The reaction mixture was diluted with ethyl acetate and water, the solids were filtered and the organic fraction was washed with water, brine and dried over Na2SO4. Filtration and solvent evaporation gave a residue which was further purified by column chromatography on silica gel, eluting with ethyl acetate/hexane with a gradient 30-50% to afford 1-[5-(3-chloro-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol (610 mg, 49.3%).

Workup

  1. filtrationthe solids were filtered
  2. washthe organic fraction was washed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationFiltration and solvent evaporation
  5. customgave a residue which
  6. customwas further purified by column chromatography on silica gel
  7. washeluting with ethyl acetate/hexane with a gradient 30-50%

Sources & evidence

ORD record
ord-1607a593369245edba7db38d6ffc3d3e
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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