2-Bromothiazole → HCID 67258522, compound

HRID 410464Notes

Reaction equation

HRID 410464 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C([Mg]Cl)(C)C.[C:12]([C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1)(=[O:14])[CH3:13]>C1COCC1>[OH:14][C:12]([C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1)([C:4]1[S:3][CH:2]=[N:6][CH:5]=1)[CH3:13]

Participants

5

Reactant 3

HCID 764302-BromothiazoleHCID 137990Methyl 4-acetylbenzoateHCID 178418918HCID 178418918, compound

Product 1

HCID 67258522HCID 67258522, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A flask was charged with 2-bromothiazole (1.386 ml, 15.55 mmol) and THF (30.6 ml) and then sealed and purged with Argon. The solution was cooled to −20° C. and isopropylmagnesium chloride (2 M, 8.16 ml, 16.32 mmol) was added drop wise. The reaction was stirred for 1 hour and then warmed to 0° C. After stirring for 60 minutes, the solution was cooled to −78° C. and methyl 4-acetylbenzoate (3.05 g, 17.10 mmol) in THF (5.11 ml) was added drop wise. The reaction stirred for an additional 30 minutes at −78° C. then warmed to room temperature. After stirring for 1 hour, the reaction was quenched with aqueous saturated NH4Cl and extracted with ethyl acetate (2×). The combined organics were dried over Na2SO4, filtered and concentrated. The crude mixture was purified by flash chromatography on silica (10-75% ethyl acetate/hexanes). The mixed fractions were combined, concentrated and re-purified by column chromatography on silica (10-75% ethyl acetate/hexanes). The desired fractions were combined and concentrated to afford methyl 4-[1-hydroxy-1-(1,3-thiazol-5-yl)ethyl]benzoate (2.54 g, 9.65 mmol, 62.0% yield). MS ESI: [M+H]+ m/z 264.0.

Workup

  1. customsealed
  2. custompurged with Argon
  3. temperaturewarmed to 0° C
  4. stirringAfter stirring for 60 minutes
  5. temperaturethe solution was cooled to −78° C.
  6. stirringThe reaction stirred for an additional 30 minutes at −78° C.
  7. temperaturethen warmed to room temperature
  8. stirringAfter stirring for 1 hour
  9. customthe reaction was quenched with aqueous saturated NH4Cl
  10. extractionextracted with ethyl acetate (2×)
  11. dry with materialThe combined organics were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude mixture was purified by flash chromatography on silica (10-75% ethyl acetate/hexanes)
  15. concentrationconcentrated
  16. customre-purified by column chromatography on silica (10-75% ethyl acetate/hexanes)
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-5c4e5b00b088441ba781a82a18f2135d
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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