4-Chlorobenzaldehyde → 4-(4-Chlorophenyl)-2-morpholin-4-yl-6-oxo-4,6-dihydrothieno[2,3-c]furan-3-carbonitrile

Temperature

-70 °C

A solution of 4-cyano-5-morpholin-4-ylthiophene-2-carboxylic acid (0.1 g, 0.42 mmol) in anhydrous THF (1.5 mL) was cooled down to −70° C. To this cooled solution was added a 2.5 M solution of n-butyl lithium in hexanes (0.672 mL, 1.68 mmol) dropwise under nitrogen. The resulting solution was stirred at −70° C. for 2 h and 4-chlorobenzaldehyde (0.142 mL, 1.26 mmol) was added. The reaction mixture was stirred at −70° C. for a further 2 h and was quenched with water. The mixture was concentrated to a small volume and the aqueous residue was washed with EtOAc. The aqueous solution was separated, acidified with 1N HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by column chromatography to give the title compound (0.020 g, 13%), LCMS: (FA) ES+ 361, 363. 1H NMR (400 MHz, d6-DMSO) δ: 7.54 (d, J=8.48 Hz, 2H), 7.38 (d, J=8.48 Hz, 2H), 6.72 (s, 1H), 3.77-3.73 (m, 4H), 3.65-3.60 (m, 4H)

1. stirringThe reaction mixture was stirred at −70° C. for a further 2 h
2. customwas quenched with water
3. concentrationThe mixture was concentrated to a small volume
4. washthe aqueous residue was washed with EtOAc
5. customThe aqueous solution was separated
6. extractionextracted with EtOAc
7. washwashed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude material was purified by column chromatography

ORD record

ord-388760b637dc4866bee0d2a18457eb52

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765746B2