Monochloramine → Quinoline

In a 25 mL 2-neck flask a solution of 18 (85 mg, 0.16 mmol) in Et2O (1.0 mL) was cooled to 0° C. and treated with a 2.5 M solution of n-butyllithium in hexanes (70 μL, 0.18 mmol, 1.0 equiv) and the reaction mixture was stirred for 15 min. A 1.0 M solution of chlorotitanium tri(isopropoxide) in hexanes (0.18 mL, 0.18 mmol, 1.0 equiv) was added and the reaction mixture was stirred at 0° C. for 15 min. A 1.0 M solution of m-chlorophenylmagnesium bromide in Et2O (0.65 mL, 0.65 mmol, 4.0 equiv) was added and the reaction mixture was stirred for 20 min. The reaction mixture was poured into saturated NH2Cl (5 mL), and extracted with EtOAc (3×4 mL). The extracts were washed with brine (1×5 mL), combined, dried (MgSO4), filtered, and concentrated. Purification by silica gel chromatography (hexane/EtOAc, 10:1) afforded 39 mg (59%) of compound 19. Data for 19: 1H NMR (400 MHz, acetone-d6): 7.55 (d, J=8.4, 1H), 7.35 (dd, J=9.9, 2.9, 1H), 7.20 (m, 4H), 6.93 (s, 1H), 6.84 (d, J=8.4, 1H), 6.81 (dd, J=8.5, 5.0, 1H), 6.73 (td, J=8.5, 2.9, 1H), 5.67 (br s, 1H), 5.49 (s, 1 H), 1.99 (s, 3 H), 1.27 (s, 3 H, 1.24 (s, 3 H); 13C NMR (100 MHz, acetone-d6): 159.2 (d, JC-F =236), 147.8, 143.5, 134.8, 134.6, 130.7, 129.9, 129.1, 128.9, 127.8, 127.1 (d, JC-F =7.9), 125.0, 119.7, 119.6, 119.4 (d, JC-F =9.0), 116.1, 114.2 (d, JC-F =24), 109.1 (d, JC-F =25), 75.7, 51.2, 29.7, 29.4, 24.1.

1. stirringthe reaction mixture was stirred at 0° C. for 15 min
2. stirringthe reaction mixture was stirred for 20 min
3. extractionextracted with EtOAc (3×4 mL)
4. washThe extracts were washed with brine (1×5 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by silica gel chromatography (hexane/EtOAc, 10:1)

ORD record

ord-c94b2c859d324302a83f8d15a666025c

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06093826