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

HRID 592732Notes

Reaction equation

HRID 592732 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

Into a solution of 167c (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 stirred at room temperature overnight. After reaction water (30 mL) was added and the resulting mixture was extracted with ethyl acetate (200 mL×3). The combined organic phase was evaporated under reduced pressure to dryness. The residue was purified by silica-gel column chromatography eluting with 20:1 methylene chloride/methanol to afford 167d 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. stirringIt was then stirred at room temperature overnight
  3. additionwas added
  4. extractionthe resulting mixture was extracted with ethyl acetate (200 mL×3)
  5. customThe combined organic phase was evaporated under reduced pressure to dryness
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 20:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-5ccb2833d4514649b04272080dc1832a
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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