Diisobutylaluminum hydride → HCID 21129381, compound

Temperature

-78 °C

To an oven-dried flask containing dry THF (10 mL) under argon at −78° C. was added a 1 M solution of (iBu)2AlH in CH2Cl2 (16.3 mL). This mixture was stirred at −78° C. for 5 min. To this was (R)-8-fluoro-5-methyl-2,3,5,6-tetrahydroazepino[4,5-b]indol-4(1H)-one (0.236 g, 1.02 mmol) in dry THF (16 mL). The reaction mixture was stirred at rt for 72 h, cooled to 0° C., then quenched by the addition of MeOH (4.5 mL). The mixture was partitioned between CH2Cl2 and 1 M aq NaO2CCH(OH)CH(OH)CO2K. The CH2Cl2 extracts were washed with brine, and dried, filtered and concentrated to give an oil. The oil was purified by silica chromatography to give the amine. To a solution of this amine (0.105 g, 0.48 mmol) in dry MeOH (4 mL) was added fumaric acid (0.028 g, 0.24 mmol) in MeOH (2.2 mL). The mixture was stirred overnight, concentrated, and the residue was dissolved in hot MeOH from which crystalline product was recovered: mp 256-258° C.; MS (ESI+) m/z 219.1; 1H NMR (CD3SOCD3, 300 MHz) δ 10.83 (1H), 9.3-8.5 (2H), 7.35 (1H), 7.01 (1H), 6.78 (1H), 6.43 (1H), 3.22-2.70 (8H), 1.30 (3H); Anal. C, 64.94; H, 6.27; N, 10.07.

1. stirringThe reaction mixture was stirred at rt for 72 h
2. temperaturecooled to 0° C.
3. customquenched by the addition of MeOH (4.5 mL)
4. customThe mixture was partitioned between CH2Cl2 and 1 M aq NaO2CCH(OH)CH(OH)CO2K
5. washThe CH2Cl2 extracts were washed with brine
6. customdried
7. filtrationfiltered
8. concentrationconcentrated
9. customto give an oil
10. customThe oil was purified by silica chromatography

ORD record

ord-c13c5b656ea64b649058ff51e007317e

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06586421B2