Water → Ethyl 3-(Cyanomethyl)-3-azatricyclo[5.2.1.02,6]deca-2(6),4-diene-4-carboxylate

HRID 1919146Notes

Reaction equation

HRID 1919146 reaction equation
[CH:1]12[CH2:10][CH:7]([CH2:8][CH2:9]1)[C:6]1[CH:5]=[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:3][C:2]2=1.[H-].[Na+].Br[CH2:19][C:20]#[N:21].O>CN(C=O)C>[C:20]([CH2:19][N:3]1[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][C:6]2[CH:7]3[CH2:10][CH:1]([CH2:9][CH2:8]3)[C:2]1=2)#[N:21]

Participants

6

Reactant 4

HCID 962WaterHCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 67016236Ethyl 4,5,6,7-tetrahydro-1H-4,7-methanoindole-2-carboxylate

Product 1

HCID 58043774Ethyl 3-(Cyanomethyl)-3-azatricyclo[5.2.1.02,6]deca-2(6),4-diene-4-carboxylateYield 72.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 334c (3.0 g, 14.6 mmol) in anhydrous DMF (30 mL) was added NaH (880 mg, 22 mmol). The mixture was stirred at room temperature for 30 minutes. 2-Bromoacetonitrile (3.5 g, 29.3 mmol) was added and the resulting mixture was heated at 65° C. for 1 hour. It was then cooled to room temperature and stirred for overnight. After reaction water (30 mL) was added and the reaction mixture was extracted with ethyl acetate (3×200 mL). The organic phase was evaporated to dryness. The residue was purified by column chromatography eluting with 20:1 methylene chloride/methanol to give 334d as a brown solid (2.6 g, 72%). MS: [M+H]+ 245.

Workup

  1. temperaturethe resulting mixture was heated at 65° C. for 1 hour
  2. temperatureIt was then cooled to room temperature
  3. stirringstirred for overnight
  4. additionwas added
  5. extractionthe reaction mixture was extracted with ethyl acetate (3×200 mL)
  6. customThe organic phase was evaporated to dryness
  7. customThe residue was purified by column chromatography
  8. washeluting with 20:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-54b9d68eb11247e5bf387c669e31c6f8
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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