5-Diethylphosphono-2-thiophenecarboxaldehyde → 3-{[5-(Diethoxy-phosphoryl)-thiophen-2-yl]-hydroxy-methyl}-5-isopropoxy-benzoic acid

Temperature

-78 °C

To a solution of 3-bromo-5-isopropoxy-benzoic acid (2.0 g, 8.26 mmol) in THF (30 ml) was added 1.6 M nBuLi (10.6 ml, 16.94 mmol) at −78° C. The reaction was stirred at −78° C. for 1 h and treated with a solution of (5-formyl-thiophen-2-yl)-phosphonic acid diethyl ester (2.5 g, 9.91 mmol) in THF. After stirring at −78° C. for 30 min, the reaction mixture was warmed up to r.t. and quenched by water, diluted with EtOAc. The aqueous layer was separated, acidified with 2N HCl to pH<1, and extracted with EtOAc (3×). The combined EtOAc layers were dried over MgSO4, filtrated, concentrated to give the crude product 3-{[5-(diethoxy-phosphoryl)-thiophen-2-yl]-hydroxy-methyl}-5-isopropoxy-benzoic acid.

1. stirringAfter stirring at −78° C. for 30 min
2. temperaturethe reaction mixture was warmed up to r.t.
3. customquenched by water
4. additiondiluted with EtOAc
5. customThe aqueous layer was separated
6. extractionextracted with EtOAc (3×)
7. dry with materialThe combined EtOAc layers were dried over MgSO4
8. filtrationfiltrated
9. concentrationconcentrated

ORD record

ord-180298702bf340e8bdb7da94082b2188

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940927B2