Hydrochloric Acid → 7'-(trifluoromethyl)spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Temperature

0 °C

To a solution of 3-(6-hydroxy-1,3-benzodioxol-5-yl)-3-(hydroxymethyl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (4.10 g, 11.7 mmol) in ethyl acetate (100.0 mL) was added tributylphosphine (3.4 mL, 2.83 g, 13.9 mmol) at 0° C. followed by the solution of di-tert-butyl azodicarboxylate (3.22 g, 13.9 mmol) in ethyl acetate (50.0 mL). The reaction solution was stirred at 0° C. for 30 min followed by the addition of 10% hydrochloric acid (50.0 mL). The reaction solution was washed with 10% hydrochloric acid (2×50.0 mL), saturated ammonium chloride (3×50 mL) and brine (3×50 mL). The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by flash chromatography to afford 7′-(trifluoromethyl)spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (3.59 g, 88%): mp 245-248° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.50 (d, J=7.9 Hz, 1H), 7.36 (d, J=7.3 Hz, 1H), 7.11 (dd, J=7.5, 7.5 Hz, 1H), 6.66 (s, 1H), 6.32 (s, 1H), 5.90 (d, J=3.1 Hz, 2H), 4.74 (ABq, 2H); 13C NMR (75 MHz, DMSO-d6) δ 179.4, 156.0, 148.9, 139.7, 134.9, 128.3, 125.8, 125.7 (m), 122.9, 119.7, 112.0, 111.4 (m), 103.6, 101.9, 93.7, 80.4, 57.5; MS (ES+) m/z 350.3 (M+1).

1. washThe reaction solution was washed with 10% hydrochloric acid (2×50.0 mL), saturated ammonium chloride (3×50 mL) and brine (3×50 mL)
2. dry with materialThe organic solution was dried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo to dryness
5. customThe residue was purified by flash chromatography

ORD record

ord-0929c3a74977468cb6282e2c806f81b5

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263606B2