Methanol → 2-(1,6-dimethyl-1H-indol-3-yl)acetonitrile
Reaction equation
CC(C)([O-])C.[K+].CC1C=CC(S([CH2:17][N+:18]#[C-])(=O)=O)=CC=1.[CH3:20][N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH3:30])[CH:28]=2)[C:23]([CH:31]=O)=[CH:22]1.CO>COCCOC>[CH3:20][N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([CH3:30])[CH:28]=2)[C:23]([CH2:31][C:17]#[N:18])=[CH:22]1Participants
Conditions
- Temperature
- -30 °C
Procedure
A suspension of potassium tert-butoxide (KOtBu) (2.21 g, 19.7 mm) in DME (30 mL) was cooled to -30° C., and treated with a solution of TosMIC (1.97 g 10.1 mm). After addition was complete, the mixture was further cooled to -60° C., treated with 1,6-dimethyl-1H-indole-3-carboxaldehyde (5.8 mm) in DME(20 mL), and stirred at that temperature for 1.5 hours. Addition of methanol (15 mL) to the cooled solution, was followed by heating to reflux temperature for 15 minutes, and evaporation of the solvent. The residue was treated with H2O (20 mL) containing acetic acid (HOAc) (0.75 mL), then extracted with CH2Cl2 (50 mL×3). The combined organic fractions were extracted with saturated NaHCO3 solution, dried over MgSO4, filtered and evaporated. Purification by flash column chromatography afforded (1,6-dimethyl-1H-indol-3-yl)-acetonitrile (0.86 g, 81%).
Workup
- additionAfter addition
- temperaturethe mixture was further cooled to -60° C.
- temperatureby heating
- temperatureto reflux temperature for 15 minutes
- customevaporation of the solvent
- additionThe residue was treated with H2O (20 mL)
- additioncontaining acetic acid (HOAc) (0.75 mL)
- extractionextracted with CH2Cl2 (50 mL×3)
- extractionThe combined organic fractions were extracted with saturated NaHCO3 solution
- dry with materialdried over MgSO4
- filtrationfiltered
- customevaporated
- customPurification by flash column chromatography
Sources & evidence
- ORD record
- ord-66560d5ecb814ea594ac00655dd06dba
- Source dataset
- uspto-grants-1999_04
- Patent number
- US05891901
Reaction notes
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