Reaction equation
[Cl:1][C:2]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:3]=1[O:4][C:5]1[S:6][CH:7]=[CH:8][N:9]=1.C([Li])CCC.[CH:21](N1CCOCC1)=[O:22]>O1CCCC1>[Cl:1][C:2]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:3]=1[O:4][C:5]1[S:6][C:7]([CH:21]=[O:22])=[CH:8][N:9]=1Participants
Conditions
- Temperature
- -78 °C
Procedure
To a solution of Example 30A (12 g, 49.9 mmol) in tetrahydrofuran (100 mL) was added butyllithium (2.5 M in hexanes, 21 mL, 52.5 mmol) drop wise over 10 minutes at −78° C. under nitrogen. The mixture was stirred at −78° C. for 1 hour, and was treated with 4-formylmorpholine (5.3 mL, 52.4 mmol) drop wise over 5 minutes. The reaction was allowed to warm to 25° C. and was stirred for 2 hours. The reaction was cooled to 0° C. and quenched with saturated NH4Cl (600 mL). The resulting mixture was extracted with ethyl acetate (2×200 mL) and the combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated to provide 13.2 g of the title compound (98%) as a light yellow liquid. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.83 (s, 3H) 7.06 (dd, J=9.19, 2.94 Hz, 1H) 7.28 (d, J=2.94 Hz, 1H) 7.57 (d, J=9.19 Hz, 1H) 8.28 (s, 1H) 9.88 (s, 1H); MS (ESI) m/z 269.9 (M+H)+.
Workup
- temperatureto warm to 25° C.
- stirringwas stirred for 2 hours
- temperatureThe reaction was cooled to 0° C.
- customquenched with saturated NH4Cl (600 mL)
- extractionThe resulting mixture was extracted with ethyl acetate (2×200 mL)
- washthe combined organic layers were washed with brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-57a6ba2da44548eabfe598692c59d55e
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08748627B2
Linked notes
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