2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → (E)-ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylate

Temperature

20 °C

LDA (24 mL of a 1.8M solution in n-C7H16-THF-PhEt, 43.3 mmol) was added dropwise to a stirred solution of DMPU (19 mL, 153.0 mmol) in anhydrous THF (100 mL) at −78° C. After 30 min, a solution of ethyl (4-methanesulfonylphenyl)-acetate (Preparation 15, 5.00 g, 20.6 mmol) in anhydrous THF (42 mL) was added dropwise. The mixture was stirred further for 1 h, before being treated dropwise with a solution of tetrahydropyran-4-carboxaldehyde (2.36 g, 20.6 mmol) in anhydrous THF (25 mL). After being allowed to warm up to 20° C. over 16 h, the reaction was quenched with saturated aqueous NH4Cl (210 mL). The THF was removed under reduced pressure, then the remainder was extracted with EtOAc (3×250 mL). The combined EtOAc extracts were dried (MgSO4), filtered, and concentrated. Column chromatography (IH-EtOAc, 7:3) furnished (E)-ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylate: m/z (ES+)=356.2 [M+NH4]+. A solution of this ester (6.46 g, 19.1 mmol) in MeOH (30 mL) and 1M NaOH (40 mL, 40.0 mmol) was heated under reflux for 1 h. On cooling, the mixture was washed with EtOAc. The aqueous phase was acidified with 1M HCl, before being extracted with EtOAc. The combined organic extracts were dried (MgSO4). Filtration and solvent evaporation afforded the title compound: m/z (ES+)=621.3 [2M+H]+.

1. customthe reaction was quenched with saturated aqueous NH4Cl (210 mL)
2. customThe THF was removed under reduced pressure
3. extractionthe remainder was extracted with EtOAc (3×250 mL)
4. dry with materialThe combined EtOAc extracts were dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated

ORD record

ord-990a4f411c084c209959cfe9b3f6014f

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07214681B2