Diisopropylamine → cis-2-(2-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione

Under a nitrogen atmosphere, a solution of monomethyl phthalate (1.31 g, 7.31 mmol) and N,N-diisopropylamine (1.72 ml, 7.31 mmol) in tetrahydrofuran (10 ml) was added dropwise to a solution of benzotriazol-1-yloxy-trispyrrolidinophosphonium hexafluorophosphate (3.77 g, 7.31 mmol) in tetrahydrofuran (10 ml) over a period of 15 minutes at room temperature. After 40 minutes, the solution thus prepared was slowly dropped into a solution of cis-2-aminocyclohexanol hydrochloride (1.0 g, 6.65 mmol) and triethylamine (1.01 ml, 7.31 mmol) in tetrahydrofuran (10 ml). After 3 hours, p-toluenesulfonic acid (35 mg) was added thereto, and the resulting mixture was refluxed. After 5 hours, water was added thereto and the resulting mixture was poured into a saturated aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) and purified again by a silica gel column chromatography (eluent: chloroform/ethyl acetate) to obtain cis-2-(2-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (1.5746 g, 97%).

1. customthe solution thus prepared
2. waitAfter 3 hours
3. temperaturethe resulting mixture was refluxed
4. waitAfter 5 hours
5. extractionextracted with ethyl acetate
6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
7. customThe organic layer dried
8. concentrationwas concentrated under reduced pressure
9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate)
10. custompurified again by a silica gel column chromatography (eluent: chloroform/ethyl acetate)

ORD record

ord-d7c1cb6757644feb94457142d968a794

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199147B2