Trifluoromethanesulfonic anhydride → (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one

Temperature

-20 °C

Prepared using general procedure 57. Under an N2 atmosphere at −20° C., diisopropyl ethyl amine (15.9 mL, 91.4 mmol) was added drop wise to a solution of solution of (R)-3-hydroxydihydrofuran-2(3H)-one (4.67 g, 45.7 mmol) in dichloromethane (70 mL). Then added trifluoromethanesulfonic anhydride (8.1 mL, 48.0 mmol) drop wise by maintaining internal temperature of the reaction mixture <−20° C. Upon completion of addition, the mixture was stirred at −20° C. for 1 hour. Then added at −20° C., 6-chloro-1,2,3,4-tetrahydroquinoline drop wise. The reaction was allowed to warm to RT over a period of 30 minutes and continued to stir at RT for 16 hrs. The reaction mixture was diluted with 200 mL of ethylacetate and washed with saturated sodium bicarbonate (3×50 mL). The organic layer was washed with a saturated aqueous NaCl solution (2×50 mL). The solution was dried over magnesium sulfate, filtered, and concentrated. Purification via silica gel chromatography using 5-50% ethyl acetate in hexane gave (S)-3-(6-chloro-3,4-dihyroquinolin-1(2H)-yl) dihydrofuran-2(3H)-one as a white solid (10.74 g, 93% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=252.3; tR=1.66 min. 1H NMR (400 MHz, DMSO-d6) δ 7.03-6.98 (m, 2H), 6.74 (d, J=8.9 Hz, 1H), 5.07 (t, J=10.0 Hz, 1H), 4.42 (t, J=9.5 Hz, 1H), 4.30-4.23 (m, 1H), 3.16-3.02 (m, 2H), 2.68 (t, J=6.4 Hz, 2H), 2.44-2.27 (m, 2H), 1.87-1.77 (m, 2H).

1. customPrepared
2. additionUpon completion of addition
3. additionThen added at −20° C.
4. temperatureto warm to RT over a period of 30 minutes
5. stirringto stir at RT for 16 hrs
6. washwashed with saturated sodium bicarbonate (3×50 mL)
7. washThe organic layer was washed with a saturated aqueous NaCl solution (2×50 mL)
8. dry with materialThe solution was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification via silica gel chromatography

ORD record

ord-752d2d07b63b40bfb506cb41856a9010

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163720B2