Hydrochloric Acid → tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Temperature

60 °C

In a scintillation vial containing 15 mL of ethanol was added Pd(OAc)2 (8.3 mg, 0.037 mmol) and DPPP (31 mg, 0.073 mmol). The reaction vessel was purged with argon, capped, and heated to 60° C. for 18 hours. To this was added tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (250 mg, 0.74 mmol) and triethyl amine(0.21 mL, 1.5 mmol) and the mixture was heated to 90° C. for 5 minutes. Butyl vinyl ether (0.2 mL, 1.5 mmol) was added and the reaction mixture was heated to 90° C. for 4 hours under argon. The reaction mixture was cooled to room temperature and 1.0 N HCl (21 mL) was added and stirred for 2 h at RT. The reaction was neutralized with sat-NaHCO3 and extracted with EtOAc. The organic phase was concentrated and the residue was purified using 40 g Redi-Sep column, eluting with 0 to 40% ethyl acetate in heptanes, to yield 0.17 g of tert-butyl 5′-acetyl-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate. H-NMR (400 MHz, CDCl3) δ ppm 7.99 (d, 1H, J=8.0 Hz), 7.82 (s, 1H), 7.57 (d, 1H, J=8.0 Hz), 5.16 (s, 2H), 4.34 (d, 2H, J=9.5 Hz), 4.15 (d, 2H, J=9.5 Hz), 2.63 (s, 3H), 1.49 (s, 9H).

1. customThe reaction vessel was purged with argon
2. customcapped
3. temperaturethe mixture was heated to 90° C. for 5 minutes
4. temperaturethe reaction mixture was heated to 90° C. for 4 hours under argon
5. temperatureThe reaction mixture was cooled to room temperature
6. extractionextracted with EtOAc
7. concentrationThe organic phase was concentrated
8. customthe residue was purified
9. washeluting with 0 to 40% ethyl acetate in heptanes

ORD record

ord-674a2eebda514eaf86eb3cf4d2e8ab0b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09420793B2