| 94% |
|
KOH (10.54 g, 188.0 mmol) was added to a solution of 4-TRIFLUOROMETHYL-LH-QUINOLIN-2- one (4.00 g, 18.8 mmol) in DMF (160 ML). After 1 hour, the mixture was treated with MeI (11.7 ML, 188.0 mmol), then stirring was continued overnight. EtOAc (200 ML) was added, followed by saturated aqueous NH4C1 to adjust the aqueous pH to 6.5. After separation of the layers, the aqueous phase was extracted further with EtOAc (2 x 200 mL). The combined organic extracts were washed with H20 (200 ML) and brine (200 mL), before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (PE-EtOAc, 4: 1 to 7: 3) yielded L-METHYL-4-TRIFLUOROMETHYL-LH-QUINOLIN-2-ONE (4.00 g, 94%): OJ ( (CD3) 2SO) = 3.65 (s, 3H), 7.10 (s, 1H), 7.40 (t, 1H), 7.65-7. 80 (m, 3H). This compound (8.70 g, 38.3 mmol) was added portionwise with stirring over 20 min to fuming H2S04 (30% oleum, 17.5 mL) at 84C. The bath temperature was raised to 120C for 1 hour, before being cooled back down to 20C. Thereupon, the mixture was added slowly to saturated aqueous NaCl (60 mL) and stirred for 30 min. The solid produced was collected & dried under vacuum at 50 C to give sodium 1-METHYL- 2-OXO-4-TRIFLUOROMETHYL-1, 2-dihydroquinoline-6-sulfonate: BH ((CD3)2SO) = 3.65 (s, 3H), 7.10 (s, 1H), 7.65 (d, 1H), 7.95 (dd, 1H), 8.00 (d, 1H). This compound was suspended in MECN- sulfolane (1: 1,52 ML), before being treated with POC13 (18.8 ML, 201.7 mmol). The mixture was heated to 88C for 1.5 hours, before being cooled to 20C over 0.5 hour. On cooling to <5C, ice cold H, ? O (128 ML) was added, the temperature being maintained below 7C. The mixture was stirred at 0C for 20 minutes, then the solid formed was collected and washed with H20 to afford, after drying, the title compound (9. 62 g, 73%): No.H (CDC13) = 3.80 (s, 3H), 7.25 (s, 1H), 7.65 (d, 1H), 8.25 (dd, 1H), 8.50 (d, 1H). |
| 94% |
|
KOH (10. 54 g, 188. 0 mmol) was added to a solution of 4-trifluoromethyl- LH-QUINOLIN-2-ONE (4. 00 g, 18. 8 mmol) in DMF (160 ML). After 1 hour, the mixture was treated with Me (11. 7 mL, 188. 0 mmol), then stirring was continued overnight. EtOAc (200 mL) was added, followed by saturated aqueous NH4Cl to adjust the aqueous pH to 6. 5. After separation of the layers, the aqueous phase was extracted further with EtOAc (2 x 200 mL). The combined organic extracts were washed with H20 (200 mL) and brine (200 mL), before being dried (MGSO4). Filtration, solvent evaporation, and column chromatography (PE- EtOAc, 4 : 1 to 7 : 3) yielded 1-METHYL-4-TRIFLUOROMETHYL-LH-QUINOLIN-2-ONE (4. 00 g, 94%) : ON ((CD3)2SO) = 3. 65 (s, 3H), 7. 10 (s, 1H), 7. 40 (t, 1H), 7. 65-7. 80 (m, 3H). THIS compound (8. 70 g, 38. 3 mmol) was added portionwise with stirring over 20 min to fuming H2SO4 (30% oleum, 17. 5 ML) at 84C. The bath temperature was raised to 120C for 1 hour, before being cooled back down to 20C. Thereupon, the mixture was added slowly to saturated aqueous NACI (60 mL) and stirred for 30 min. The solid produced was collected & dried under vacuum at 50 C to give sodium 1-methyl-2-oxo-4-trifluoromethyl-1, 2- dihydroquinoline-6-sulfonate : ON ((CD3)2SO) = 3. 65 (s, 3H), 7. 10 (S, 1H), 7. 65 (d, 1H), 7. 95 (dd, 1H), 8. 00 (d, 1EI). This compound was suspended in MECN- sulfolan (1 : 1, 52 ML), before being treated with POC13 (18. 8 mL, 201. 7 mmol). The mixture was heated to 88C for 1. 5 hours, before being cooled to 20C over 0. 5 hour. On cooling to <5C, ice cold H20 (128 ML) was added, the temperature being maintained below 7C. The mixture was stirred at 0C for 20 minutes, then the solid formed was collected and washed with H2O to afford, after drying, the title compound (9. 62 g, 73%) : No.H (CDCL3) = 3. 80 (s, 3H), 7. 25 (s, 1H), 7. 65 (d, 1H), 8. 25 (dd, 1H), 8. 50 (d, 1H). |
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