Formaldehyde → 7-CHLORO-2-VINYLQUINOLINE

Temperature

-20 °C

A stirred solution of diisopropylamine (2.24 ml, 15.97 mmol) in tetrahydrofuran (15.0 ml) at −10° C. under nitrogen was treated dropwise with a 2.5 M solution of n-butyllithium in hexane (6.4 ml, 15.97 mmol). After stirring below 0° C. for 30 min the pale yellow solution was cooled to −20° C. and a solution of diethyl 7-chloro-2-quinolylmethylphosphonate (5.0 g, 15.97 mmol) in tetrahydrofuran was added dropwise. The resulting dark green solution was stirred below 0° C. for 1 h, cooled to −10° C. and treated with paraformaldehyde (0.53 g, 17.57 mmol) in portions. Stirred cold for 15 min after which the cooling bath was removed and the mixture was stirred at 25° C. for 90 min. Quenched with brine (300 ml), extracted into ethyl acetate (3×100 ml), the combined organic extracts were washed with brine (3×200 ml), dried (Na2SO4) and the solvent was removed in vacuo to give a dark brown solid. Column chromatography (ethyl acetate-light petroleum (b.p. 40-60° C.), 1:19) provided the title compound (1.80 g, 59%) as pale yellow crystals. Crystallised from ethyl acetate and light petroleum (b.p. 40-60° C.) as cream crystals, m.p. 79.7-80° C. (Found: C, 69.84; H, 4.15; N; 7.25; Cl, 18.91. C11H8ClN requires C, 69.67; H, 4.25; N, 7.39; Cl, 18.69%); νmax (nujol)/cm−1 1628, 1609; δH (270 MHz) 5.67 (1H, dd, 2′-H, 3J2′,1′=10.89, 2J2′,2″=1.0 Hz); 6.29 (1H, dd, 2″-H, 3J2″,1′=17.7, 2J2″,2′=0.8 Hz); 7.02 (1H, dd, 1′-H, 3J1′,2″=17.5, 3J1′,2′=10.9 Hz); 7.42 (1H, dd, 7-H, Jo=8.8, Jm=2.1 Hz); 7.53 (1H, d, 3-H, Jo=8.9 Hz); 7.66 (1H, d, 5-H, Jo=8.9 Hz); 8.03 (1H, d, 4-H, Jo=8.3 Hz); 8.05 (1H, s, 8-H). δc (67.8 MHz) 118.6 (2′-C); 120.5 (3-C); 125.7 (4a-C); 135.3 (7-C); 136.0 (4-C); 137.5 (1′-C); 148.3 (8a-C); 156.9 (2-C). Remaining signals fall in the range 127.1-128.5 ppm; m/z 191.0, 189.0 (33.48, 100, M+), 165.0, 163.0 (21.89, 65.87), 154.0 (5.13), 128.1 (9.14).

1. stirringThe resulting dark green solution was stirred below 0° C. for 1 h
2. temperaturecooled to −10° C.
3. stirringStirred cold for 15 min after which the cooling bath
4. customwas removed
5. stirringthe mixture was stirred at 25° C. for 90 min
6. customQuenched with brine (300 ml)
7. extractionextracted into ethyl acetate (3×100 ml)
8. washthe combined organic extracts were washed with brine (3×200 ml)
9. dry with materialdried (Na2SO4)
10. customthe solvent was removed in vacuo
11. customto give a dark brown solid

ORD record

ord-9e08204d05a340b1902bd43a150f0685

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06509476B1