2-Cyanobenzaldehyde → HCID 67044786, compound

HRID 2367093Notes

Reaction equation

HRID 2367093 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:6]=[CH:5]2.C([Li])CCC.[C:24]([C:26]1[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=1[CH:28]=[O:29])#[N:25]>O1CCCC1>[OH:29][CH:28]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:6]=[CH:5]2)[C:27]1[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=1[C:24]#[N:25]

Participants

5

Reactant 3

HCID 1012092-CyanobenzaldehydeHCID 67044778HCID 67044778, compoundHCID 178418339Butyllithium

Product 1

HCID 67044786HCID 67044786, compoundYield 61.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-indole (0.96 g, 2.9 mmol) in tetrahydrofuran (30 mL) cooled to −78° C. was added n-butyllithium (1.6 M in hexanes, 2.2 mL, 3.5 mmol). After stirring for 15 min at −78° C., 2-cyanobenzaldehyde (0.58 g, 4.4 mmol in 2 mL tetrahydrofuran) was quickly added. After stirring for 30 min at −78° C. and allowing to warm to room temperature, the reaction mixture was quenched with an excess of saturated aqueous ammonium chloride solution, then diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted (2×100 mL ethyl acetate). The combined organic layers were dried (sodium sulfate), filtered and concentrated in vacuo. Column chromatography (silica gel, 1:1 hexanes/ethyl acetate) gave 0.68 g (61%) of 2-{hydroxy[1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-indol-5-yl]methyl} benzonitrile. 1H NMR (400 MHz, CDCl3): 7.99 (d, 1H), 7.60 (d, 1H), 7.57 (m, 2H), 7.53 (d, 1H), 7.27 (m, 2H), 7.10 (dd, 1H), 6.56 (m, 2H), 5.52 (s, 2H), 3.50 (m, 2H), 0.51 (m, 2H), 0.00 (s, 9H); MS (EI) for C22H26N2O2Si: 379 (MH+).

Workup

  1. stirringAfter stirring for 30 min at −78° C.
  2. temperatureto warm to room temperature
  3. customthe reaction mixture was quenched with an excess of saturated aqueous ammonium chloride solution
  4. additiondiluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted (2×100 mL ethyl acetate)
  7. dry with materialThe combined organic layers were dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9f91b4ee21340e0a38d988365875946
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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