Hexamethylphosphoramide → HCID 66862364, compound

Temperature

-78 °C

A 2.0 M solution of LDA in heptane/THF/ethylbenzene (1.61 mL, 3.21 mmol) was added in a dropwise manner to a solution of 7-methoxy-isothiochroman-4-one (0.50 g, 2.57 mmol) in THF (50 mL) at −78° C. under N2. After 30 min at −78° C. HMPA (0.46 g, 2.57 mmol) and methyl cyanoformate (0.27 g, 3.21 mmol) were added and the yellow solution was allowed to stir at −78° C. for 30 min. The solution was then allowed to warm to room temperature and a saturated solution of NH4Cl (100 mL) was added. The slurry was extracted with EtOAc (3×75 mL) and the organic extracts were combined, dried (MgSO4) and concentrated under reduced pressure to provide a bright yellow oil. The oil was purified on silica using medium pressure chromatography (9:1 petroleum ether/EtOAc) to provide 7-methoxy-isothiochroman-4-one-3-carboxylic acid methyl ester as a bright yellow oil (0.51 g, 78%). 1H-NMR (300 MHz, CDCl3) δ 3.73 (s, 2H), 3.83 (s, 3H), 3.85 (s, 3H), 6.67 (d, J=3 Hz, 1H), 6.45 (dd, J=3, 8.7 Hz, 1H), 7.80 (d, J=8.7 Hz, 1H), 12.52 (s, 1H).

1. temperatureto warm to room temperature
2. extractionThe slurry was extracted with EtOAc (3×75 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated under reduced pressure
5. customto provide a bright yellow oil
6. customThe oil was purified on silica using medium pressure chromatography (9:1 petroleum ether/EtOAc)

ORD record

ord-b67477b85d994bd3a731592d9c418a95

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07872023B2