Dimethylformamide → 5-Methoxy-2-methyl-1H-indole-3-carbonitrile

HRID 889901Notes

Reaction equation

HRID 889901 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[CH:6]2.[C:13](#[N:15])C.ClS(N=C=O)(=O)=O.CN(C)C=O>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[C:13]#[N:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6342AcetonitrileHCID 706425-Methoxy-2-methylindoleHCID 70918Chlorosulfonyl isocyanate

Product 1

HCID 222500905-Methoxy-2-methyl-1H-indole-3-carbonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 0° C. solution of 5-Methoxy-2-methyl-1H-indole (5 g, 31.0 mmol), dry acetonitrile, (90 mL) was slowly added chlorosulfonyl isocyanate (3 mL, 34.1 mmol). The reaction was stirred and allowed to warm to room temperature and stirred for an additional four hours followed by the addition of dimethyl formamide (4.8 mL (62.0 mmol)and then stirred for an additional 1.5 hours at room temperature. The reaction was poured into water and extracted with diethyl ether. The aqueous layer was adjusted to pH 9 with 1M potassium carbonate, and extracted with diethyl ether. The ether layers were combined and dried over magnesium sulfate, filtered and concentrated. Crystallization of the residue from ether and hexane gave 5-methoxy-2-methyl-1H-indole-3-carbonitrile (3.86 g) in 67% yield as a light pink solid. C11H10N2O: GC/MS r.t.=4.06 min., m/z 186; 1H NMR (CDCl3): δ 7.22 (d, 1H, J=8.3 Hz), 7.08 (s, 1H), 6.86 (d, 1H, J=8.3 Hz), 3.86 (s, 3H), 2.60 (s, 3H) ppm.

Workup

  1. customTo a 0° C.
  2. stirringstirred for an additional four hours
  3. stirringstirred for an additional 1.5 hours at room temperature
  4. extractionextracted with diethyl ether
  5. extractionextracted with diethyl ether
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrystallization of the residue from ether and hexane

Sources & evidence

ORD record
ord-ef16703b86734a708b928469a1eba742
Source dataset
uspto-grants-2006_02
Patent number
US06995171B2

Reaction notes

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