Borane → 7-Methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine

Into a 1-neck round-bottom flask, to 8-methoxy-1,3,4,5-tetrahydro-benzo[d]azepin-2-one (30.00 g, 0.16 mol) in tetrahydrofuran (200 mL) was added a 1 M solution of borane in tetrahydrofuran (450 mL) via cannula at 0° C., under an atmosphere of nitrogen. After 20 minutes the reaction was allowed to warm to room temperature and then the flask was equipped with a condenser and the reaction was heated at reflux overnight. The reaction was quenched by careful addition of concentrated aqueous HCl (37%). The tetrahydrofuran was removed in vacuo and to the aqueous reaction mixture was added an additional 50 mL of concentrated HCl and the resulting mixture was refluxed for 3 h, cooled and neutralized with 33% NaOH to pH 7-8 and further with saturated Na2CO3 to pH 11. The mixture was extracted three times with ethyl acetate, and the combined extracts were dried (MgSO4), and concentrated. The crude product was passed through a short SiO2 plug (MeOH/DCM 0-15%) to provide 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (17 g, 55%). 1H-NMR (CDCl3) δ 7.01 (d, J=8.3 Hz, 1H), 6.68 (d, J=2.5 Hz, 1H), 6.65 (dd, J=2.5, 8.1 Hz, 1H), 3.79 (s, 3H), 2.96 (m, 4H), 2.88 (m, 4H), 2.50 (br s, 1H); LC/MS (ESI+): 178.05 (M+H).

1. customthe flask was equipped with a condenser
2. temperaturethe reaction was heated
3. temperatureat reflux overnight
4. customThe reaction was quenched by careful addition of concentrated aqueous HCl (37%)
5. customThe tetrahydrofuran was removed in vacuo and to the aqueous reaction mixture
6. additionwas added an additional 50 mL of concentrated HCl
7. temperaturethe resulting mixture was refluxed for 3 h
8. temperaturecooled
9. extractionThe mixture was extracted three times with ethyl acetate
10. dry with materialthe combined extracts were dried (MgSO4)
11. concentrationconcentrated

ORD record

ord-941be038eb20416886cde00620554aa4

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552186B2