Citric Acid → HCID 117925652, compound

To a solution of 3-ethylbenzo[de]isochromen-1 (3H)-one (0.55 g) in dichloromethane (7 mL) at −78° C. was added diisobutylaluminum hydride (2.19 mL, 20% solution in toluene). After 3 hours 10% solution aqeuous solution of citric acid (10 mL) was added and the mixture was stirred for 15 minutes at room temperature. Phases were separated and the aqueous phase was extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with brine, dried with Na2SO4 and concentrated. The purification of evaporation residue by column chromatography (ethyl acetate-heptanes) afforded 3-ethyl-1,3-dihydrobenzo[de]isochromen-1-ol (0.22 g, mixture of diastereomers) that was dissolved in dichloromethane (5 mL). Solution was cooled to 0° C. and trimethylsilyl cyanide (0.39 mL) was added, followed by boron trifluoride triethyl etherate (0.26 mL). After 2.5 hours saturated solution of NaHCO3 (10 mL) was added and the mixture was extracted with dichloromethane. Combined organic phases were washed with brine, dried (Na2SO4) and concentrated. The evaporation residue containing the mixture of diastereomers of 3-ethyl-1,3-dihydrobenzo[de]isochromene-1-carbonitrile (170 mg) was mixed with dioxane (2 mL) and 10% aqueous solution of NaOH (1.6 mL) was added and the mixture was heated to reflux. After 13 hours, reaction mixture was cooled to room temperature and water (10 mL) and dichloromethane (10 ml) were added. Aqueous phase was acidified with 4M HCl and extracted with EtOAc (3×10 mL). Combined organic phases were washed with brine, dried with Na2SO4 and concentrated. The evaporation residue containing the 3-ethyl-1,3-dihydrobenzo[de]isochromene-1-carboxylic acid (80 mg) was turned to the title compound using synthesis methods A2 and A3 along with the separation method E in A3. The obtained 2-(3-ethyl-1,3-dihydrobenzo[de]isochromen-1-yl)-4,5-dihydro-1H-imidazole was converted to the title compound using salt formation method A. (Yield 5.7 mg).

1. customPhases were separated
2. extractionthe aqueous phase was extracted with ethyl acetate (2×10 mL)
3. washThe combined organic phases were washed with brine
4. dry with materialdried with Na2SO4
5. concentrationconcentrated
6. customThe purification of evaporation residue by column chromatography (ethyl acetate-heptanes)

ORD record

ord-7c2518e1c30d441989e6115eec07373d

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249127B2