Hydrochloric Acid → HCID 67946568, compound

To a 0° C. mixture of 980 mg (8.04 mmol) 4-(N,N-dimethylamino)pyridine, 1.25 g (6.04 mmol) of 4-piperidinobutyric acid hydrochloride and 2.00 g (5.04 mmol) of the trans-title product of Example 181 in 10 ml of dichloromethane was added 1.14 g (5.54 mmol) of dicyclohexyl carbodiimide. The resultant mixture was stirred for 15 hours at 25° C. and then filtered. The filtrate was evaporated and the residue purified via column chromatography on 150 g of silica gel eluted with 10% methanol-dichloromethane to give an oil. This oil was dissolved in ethanol and acidified with 10.1 ml of lN hydrochloric acid. The solvent was removed on a rotating evaporator and the residue crystallized from dichloromethane-diisopropyl ether to give 2.97 g (95%) of present title compound, m.p. 145°-150° C. 1H-NMR(CDCl3, 300 MHz)delta(ppm): 1.25 (m,), 1.8 (m), 2.22 (m), 2.38 (m), 2.47 (dd, J=14, 9 Hz, 1H), 2.60 (dd, J=12, 6 Hz, 1H), 2.81 (m), 2.9-3.2 (m), 3.46 (m), 3.99 (dd, J=12, 2 Hz, 1H), 4.04 (dd, J=12, 2 Hz, 1H), 5.64 (d, J=3 Hz, OCH), 5.76 (d, J=20 Hz, 1H), 5.82 (d, J=20 Hz, 1H), 6.81 (d, J=8 Hz, ArH), 6.96 (m, 2ArH), 7.1-7.3 (m, 5ArH), 7.82 (dd, J=8, 8 Hz, ArH), 8.01 (dd, J=8, 8 Hz, ArH), 8.08 (d, J=8 Hz, ArH), 8.12 (d, J=8 Hz, ArH) and 8.82 (m, 2ArH).

1. filtrationfiltered
2. customThe filtrate was evaporated
3. customthe residue purified via column chromatography on 150 g of silica gel
4. washeluted with 10% methanol-dichloromethane
5. customto give an oil
6. customThe solvent was removed on a rotating evaporator
7. customthe residue crystallized from dichloromethane-diisopropyl ether

ORD record

ord-44d35996d5d645b7a84c0ea09ea91fbf

Source dataset

uspto-grants-1991_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05059609