4-Methoxyphenylacetic Acid → HCID 58438475, compound

Participants

Reaction Steps

A mixture of 2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane dihydrochloride (3-1e, 600 mg, 1.40 mmol), p-methoxyphenylacetic acid (232 mg, 1.40 mmol), HBTU (529 mg, 1.40 mmol) and triethylamine (1.2 mL, 8.6 mmol) in 5 mL of DMF was stirred at room temperature for 20 hours. The solvent was removed in vacuo, the residue was azeotroped with toluene and partitioned between 1N NaOH (50 mL) and ethyl acetate (50 mL). The organic layer was washed with brine, dried (Na2SO4) and concentrated. The crude product was purified on an Analogix (Analogix Inc., Burlington, Wis.) 24 g silica column (1-15% MeOH in DCM in 30 minutes) to give the product as a light foam. This solid was stirred with diethyl ether (80 mL) for 18 h and filtered to give the title compound as a light grey solid (540 mg, 82%). MS (ES+) 469.5 (M+H)+ 1H NMR (CDCl3) δ 1.52-1.58 (m, 2H), 1.65-1.72 (m, 2H), 1.87-1.95 (m, 1H), 2.12-2.21 (m, 1H), 2.82-2.90 (m, 1H), 3.02-3.15 (m, 5H), 3.33 (t, 2H), 3.52 (t, 2H), 3.65 (s, 2H), 3.78 (s, 3H), 3.94-3.97 (m, 1H), 6.82-6.87 (m, 2H), 7.12-7.17 (m, 3H), 7.35 (d, 1H), 8.24 (d, 1H), 8.28 (s, 1H), 8.78 (d, 2H). [α]D20=+43.2 deg (c=8 mg/mL, MeOH).

Provenance & Evidence