Cyclohexyl isocyanide → HCID 178455701, compound

1-(3-isopropoxybenzyl)-2-vinylpiperidin-4-one (7.00 g, 25.6 mmol) in methanol (14 ml) was added cyclohexyl isocyanide (3.17 ml, 25.6 mmol) then potassium cyanate (2.08 g, 25.6 mmol) in water (5 ml) was added. 3-Fluoroaniline hydrochloride (3.78 g, 25.6 mmol) was then added at 0° C. The mixture was stirred at rt for 12 hrs. The reaction was incomplete and another half equivalent of cyclohexyl isocyanide (1.59 ml, 12.8 mmol), potassium cyanate (1.04 g, 12.8 mmol), and 3-fluoroaniline hydrochloride (1.89 g, 12.8 mmol) was added. The mixture stirred for an additional twelve hours. The solution was concentrated and purified on silica gel 7% methanol/chloroform with 0.1% triethylamine. The impure product was purified a second time by flash chromatography on silica gel starting with 50% ethyl acetate/hexanes to 100% ethyl acetate. The diastereomers were resolved on a Chiral AD column 10% ethanol/hexanes with 0.3% diethylamine 250 ml/min at 250 nm.

1. stirringThe mixture stirred for an additional twelve hours
2. concentrationThe solution was concentrated
3. custompurified on silica gel 7% methanol/chloroform with 0.1% triethylamine
4. customThe impure product was purified a second time by flash chromatography on silica gel starting with 50% ethyl acetate/hexanes to 100% ethyl acetate

ORD record

ord-d57fd99f377a42fe926833ef7ecc89ab

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211904B2