Methyl 4-Formylbenzoate → Methyl 4-(hydroxy(thiazol-2-yl)methyl)benzoate

Temperature

-20 °C

2-Bromothiazole (2.72 ml, 30.5 mmol) was taken up in THF (60 ml) and cooled to −20° C. Isopropylmagnesium chloride (16.00 ml, 32.0 mmol) was added drop wise. After stirring for 1 h (−10° C. to 0° C.), the reaction was cooled to −78° C., and methyl 4-formylbenzoate (5.50 g, 33.5 mmol) in THF (10 ml) was added drop wise. The reaction was stirred for 30 min at −78° C., then warmed to room temperature. After 1 h at room temperature, the reaction was quenched with aqueous saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (10-75% EtOAc/hexanes) to provide methyl 4-[hydroxy(1,3-thiazol-2-yl)methyl]benzoate (7.29 g, 29.2 mmol, 96% yield) as an off-white solid. MS ESI: [M+H]+ m/z 250.0.

1. temperaturethe reaction was cooled to −78° C.
2. stirringThe reaction was stirred for 30 min at −78° C.
3. temperaturewarmed to room temperature
4. waitAfter 1 h at room temperature
5. customthe reaction was quenched with aqueous saturated NH4Cl
6. extractionextracted with EtOAc (2×)
7. dry with materialThe combined organic layers were dried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash chromatography (10-75% EtOAc/hexanes)

ORD record

ord-93d297143f4a492b831d0f69fca00238

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08551984B2