Water → 2-(8-Fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxobutanenitrile
Reaction equation
[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[CH:5]=[C:4]([CH2:12][C:13]#[N:14])[CH:3]=1.[H-].[Na+].[C:17](OCC)(=[O:19])[CH3:18].O>C1COCC1>[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[CH:5]=[C:4]([CH:12]([C:17](=[O:19])[CH3:18])[C:13]#[N:14])[CH:3]=1Participants
Conditions
- Temperature
- 60 °C
Procedure
To a solution of (8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)acetonitrile (0.40 g, 2.10 mmol) in THF (10 mL) was added sodium hydride (60% dispersion in mineral oil, 0.25 g, 6.3 mmol) and ethyl acetate (2.05 ml, 21.0 mmol) and the mixture was stirred at 60° C. for 2 h. After cooling to 0° C., water was added (25 mL) and the aqueous layer was washed with dichloromethane (3×15 mL), acidified with 1N HCl to pH 3 and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with brine (30 mL) then dried with sodium sulfate, filtered and concentrated to give 2-(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxobutanenitrile as an orange solid (0.37 g; 75% yield). 1H NMR (400 MHz, d6-DMSO) δ 7.05 (dd, 1H), 6.93 (br. s, 1H), 4.30 (m, 5H), 2.30 (s, 3H).
Workup
- temperatureAfter cooling to 0° C.
- washthe aqueous layer was washed with dichloromethane (3×15 mL)
- extractionextracted with ethyl acetate (3×25 mL)
- washThe combined organic extracts were washed with brine (30 mL)
- dry with materialthen dried with sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-742d9b44bb204b00851aa0d768b3b3af
- Source dataset
- uspto-grants-2011_01
- Patent number
- US07872014B2
Reaction notes
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