Dimethylformamide → 5-Chloro-1-(4-fluorophenyl)indol-3-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[CH:11]=[CH:10]2.[OH-].[Na+].CN(C)[CH:27]=[O:28]>>[Cl:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[CH:11]=[C:10]2[CH:27]=[O:28]Participants
Procedure
Phosphorus oxychloride (12.5 g, 0.081 mol) was added to N,N-dimethylformamide (29.5 g, 0.19 mol) at 0°-5° C. After stirring for 10 minutes a solution of 5-chloro-1-(4-fluorophenyl)indole (20 g, 0.081 mol) in N,N-dimethylformamide (50 mL) was added at 0°-5° C. The reaction mixture was stirred for 0.5 h and subsequently poured into ice. The resulting mixture was made alkaline with concentrated NaOH and after stirring for 1 h at room temperature the mixture was extracted with diethyl ether (2×250 mL). The combined organic phases were dried (Na2SO4),the solvents evaporated and the remaining oil was purified by column chromatography (eluted with ethyl acetate/heptane 1:1) affording pure title compound 20.1 g (90%) which crystalized from heptane: mp 152°-154° C.; 1H NMR (CDCl3) δ 7.20-7.35 (m, 4 H), 7.50 (dd, 2 H), 7.85 (s, 1 H), 8.35 (s, 1 H), 10.05 (s, 1 H). Anal. (C15H9NO) C, H, N.
Workup
- additionwas added at 0°-5° C
- additionsubsequently poured into ice
- stirringafter stirring for 1 h at room temperature the mixture
- extractionwas extracted with diethyl ether (2×250 mL)
- customevaporated
- customthe remaining oil was purified by column chromatography (eluted with ethyl acetate/heptane 1:1)
Sources & evidence
- ORD record
- ord-bb315075c240469593724ced6588d5d8
- Source dataset
- uspto-grants-1998_08
- Patent number
- US05789404
Reaction notes
Loading…