4-Methylmorpholine → HCID 22719739, compound

Temperature

90 °C

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (122 mg, 0.64 mmol), 1-hydroxybenzotriazole hydrate (86 mg, 0.64 mmol) and 4-methylmorpholine (173 μl, 1.59 mmol) were added sequentially to a cooled solution of 1-{2-[(benzyloxy)carbonyl]4-phenylbutyl}cyclopentane-carboxylic acid (EP 274234) (202 mg, 0.53 mmol) in N,N-dimethylformamide (5 ml) at room temperature, followed by the amine hydrochloride from preparation 6 (6/23) (146 mg, 1.06 mmol), and the reaction stirred at 90° C. for 18 hours. The cooled solution was concentrated under reduced pressure and the residue partitioned between water (20 ml) and ethyl acetate (100 ml). The layers were separated, the organic phase washed with water (3×30 ml), brine (25 ml) dried (MgSO4), and evaporated under reduced pressure to give a clear oil. The crude product was purified by column chromatography on silica gel using dichloromethane:methanol (98:2) as eluant to afford the title compound as a colourless oil, 162 mg, 67%; 1H NMR (CDCl3, 400 MHz) δ: 1.38-1.53 (m, 2H), 1.53-1.96 (m, 8H), 2.02 (m, 2H), 2.27 (t, 2H), 2.46 (m, 3H), 2.76 (d, 3H), 3.44 (m, 2H), 5.13 (s, 2H), 5.79 (bs, 1H), 6.38 (m, 1H), 7.06 (d, 2H), 7.18 (m, 1H), 7.22 (m, 2H), 7.38 (m, 5H); LRMS: m/z 465.5 (MH+).

1. concentrationThe cooled solution was concentrated under reduced pressure
2. customthe residue partitioned between water (20 ml) and ethyl acetate (100 ml)
3. customThe layers were separated
4. washthe organic phase washed with water (3×30 ml), brine (25 ml)
5. dry with materialdried (MgSO4)
6. customevaporated under reduced pressure
7. customto give a clear oil
8. customThe crude product was purified by column chromatography on silica gel

ORD record

ord-3886bc4340a545a88a19d7b9b1ac2ee3

Source dataset

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06734186B1