Thiazole → HCID 68720433, compound

HRID 885106Notes

Reaction equation

HRID 885106 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[O:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1.Br[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][N:20]=1>O1CCCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:25]([C:22]1[CH:23]=[CH:24][C:19]([C:5]2[S:1][C:2]([C:14]3([OH:17])[CH2:15][CH2:16][O:11][CH2:12][CH2:13]3)=[N:3][CH:4]=2)=[N:20][CH:21]=1)([O-:27])=[O:26]

Participants

8

Reactant 4

HCID 9256ThiazoleHCID 782402-Bromo-5-nitropyridineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 178418339Butyllithium2×

Product 1

HCID 68720433HCID 68720433, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a cold (−78° C.) solution of thiazole (0.382 mL, 5.41 mmol) in tetrahydrofuran (30 mL) was added n-butyllithium (3.38 mL, 5.41 mmol, 1.6 M in hexane) dropwise. After 15 minutes, dihydro-2H-pyran-4(3H)-one (0.49 mL, 5.41 mmol) was added in a single portion. After 30 minutes, n-butyllithium (3.38 mL, 5.41 mmol, 1.6 M in hexane) was added dropwise. The reaction was allowed to stir for an additional 20 minutes, after which ZnCl2 (10.8 mL, 10.8 mmol, 1 M in diethyl ether) was added. The cooling bath was removed, and the reaction warmed to room temperature. 2-Bromo-5-nitropyridine (1.10 g, 5.41 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.623 g, 0.54 mmol) were added, and the reaction heated to 55° C. for 16 h. The reaction was cooled to ambient temperature and quenched by the addition of saturated NH4Cl (30 mL) and ethyl acetate (30 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×30 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on SiO2, eluting with a gradient of 10% ethyl acetate in hexane to 35% ethyl acetate in hexane, to give the title product. MS (ESI) m/z 308 [M+H]+.

Workup

  1. waitAfter 30 minutes
  2. customThe cooling bath was removed
  3. temperaturethe reaction heated to 55° C. for 16 h
  4. temperatureThe reaction was cooled to ambient temperature
  5. customquenched by the addition of saturated NH4Cl (30 mL) and ethyl acetate (30 mL)
  6. customThe layers were separated
  7. extractionthe aqueous was extracted with additional ethyl acetate (2×30 mL)
  8. dry with materialThe combined organics were dried with anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on SiO2
  12. washeluting with a gradient of 10% ethyl acetate in hexane to 35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b4146fb7cb524c1eb5028071f76a8c8d
Source dataset
uspto-grants-2012_08
Patent number
US08242139B2

Reaction notes

Loading…