Hydrochloric Acid → HCID 58487588, compound

A solution of 12a (400 mg, 1.82 mmol) in formic acid (3 mL) and 37% formaldehyde (3 mL) was heated to 85° C. for 30 minutes. The cooled mixture was slowly added to a rapidly stirred mixture of saturated potassium carbonate (15 mL) and dichloromethane (20 mL). The aqueous layer was extracted again (3×20 mL) with dichloromethane. The organic layer was concentrated and the residue chromatographed over silica gel (6 g) with 8% methanol in dichloromethane to provide 190 mg of clear, pale amber oil. The free base was converted to the HCl salt in isopropanol by the addition of excess HCl-EtOH. The resulting solution was concentrated and the residue was crystallized from isopropanol-ethyl acetate (1:3) to afford 13 (100 mg) as a white solid. An analytical sample was obtained by recrystallization twice more from isopropanol-ethyl acetate. MS (ESI) m/z 198 [M+1]+. 1H NMR (CDCl3) δ 1.55-1.70 (m, 1H), 1.90-2.05 (m, 2H), (bd, 1H), 2.58 (s, 3H), 2.77 (s, 3H), 2.95 (bs, 1H), 3.15-3.26 (m, 1H), 3.41-3.44 (d, 1H), 3.71-3.74 (d, 1H), 3.83 (t, 1H), 10.87 (bs, 1H).

1. extractionThe aqueous layer was extracted again (3×20 mL) with dichloromethane
2. concentrationThe organic layer was concentrated
3. customthe residue chromatographed over silica gel (6 g) with 8% methanol in dichloromethane
4. customto provide 190 mg of clear, pale amber oil
5. concentrationThe resulting solution was concentrated
6. customthe residue was crystallized from isopropanol-ethyl acetate (1:3)

ORD record

ord-ce32c45bbf16426f9f7429a422556aad

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853219B2