Reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[CH2:11]([Li])[CH2:12]CC.CN(C)CCN(C)C.ICC.[NH4+].[Cl-]>C1COCC1>[CH2:11]([C:3]1[C:2](=[O:10])[N:1]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]2)[CH3:12]Participants
Procedure
A solution of oxindole (40 g, 0.3 mol) in dry THF (400 ml) under N2 was cooled to −25° C. and treated drop wise with n-butyl lithium (2.5M in hexanes, 240 ml, 0.6 mol). To the resulting solution was added N,N,N′,N′-tetramethylethylenediamine (90.4 ml, 0.6 mol). After 30 min. iodoethane (48 ml, 0.6 mol) was added and the reaction mixture was allowed to warm to RT and stirred over night. The reaction mixture was poured into aqueous NH4Cl solution, extracted with EtOAc (2×) and the combined organic layers were washed with dil. HCl, water, brine, dried (MgSO4) and concentrated. The residual oil was triturated with hexane to afford the crude product (24.5 g, 51%). A sample (3 g) was recrystallized from EtOAc/hexane to obtain the title compound (1.4 g), m.p. 100-101° C.; 1H-NMR (DMSO-d6) δ 0.76 (t, 3H, J=7.5 Hz), 1.8-2.0 (m, 2H), 3.38 (t, 3H, J=5.7 Hz), 6.8 (dt, 1H, J=7.69, 0.45 Hz), 6.93 (dt, 1H, J=7.45, 1.10 Hz), 7.15 (m, 1H), 7.22 (m, 1H), 10.3 (s, 1H); MS (ESI) m/z 270 [M+H].
Workup
- extractionextracted with EtOAc (2×)
- washthe combined organic layers were washed with dil. HCl, water, brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
- customThe residual oil was triturated with hexane
- customto afford the crude product (24.5 g, 51%)
- customA sample (3 g) was recrystallized from EtOAc/hexane
Sources & evidence
- ORD record
- ord-3dbdb1327767469bb15e924a3a8e16e7
- Source dataset
- uspto-grants-2003_08
- Patent number
- US06608068B2
Linked notes
Loading…