Sodium hydride → 2-Fluoro-6-hydroxy-4-(3-thienylmethoxy)benzaldehyde

Temperature

0 °C

Sodium hydride (0.52 g, 60% dispersion in mineral oil) is added portionwise over 30 minutes to a solution of 2,4-dihydroxy-6-fluorobenzaldehyde (2 g) in DMF (50 mL) at 0° C. The mixture is stirred at 0° C. for 30 minutes then a solution of 3-chloromethylthiophene (1.72 g) in DMF (50 mL) is added and the mixtured stirred at 60° C. for 16 hours. The reaction is concentrated in vacuo and the residue partitioned between diethyl ether (50 mL) and water (50 mL). The aqueous phase is extracted four times with diethyl ether (50 mL) and the combined organic phases washed with brine (50 mL). The organic phase is dried over magnesium sulphate, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:4 v/v). Fractions homogeneous in the required product are combined and evaporated to give a pale yellow solid which is triturated with diisopropyl ether to give 6-fluoro-2-hydroxy-4-(3-thienylmethoxy)benzaldehyde (1.1 g) as a yellow solid.

1. stirringthe mixtured stirred at 60° C. for 16 hours
2. concentrationThe reaction is concentrated in vacuo
3. customthe residue partitioned between diethyl ether (50 mL) and water (50 mL)
4. extractionThe aqueous phase is extracted four times with diethyl ether (50 mL)
5. washthe combined organic phases washed with brine (50 mL)
6. dry with materialThe organic phase is dried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:4 v/v)
10. customevaporated
11. customto give a pale yellow solid which
12. customis triturated with diisopropyl ether

ORD record

ord-e5bc304d34d049f18f9086e4368f7c0e

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06211234B1