N-methyl-2-pyrrolidone → Isoquinoline-7-carbonitrile

HRID 14254Notes

Reaction equation

HRID 14254 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:12][N:13]1C(=O)CCC1>>[C:12]([C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[CH:9]2)=[CH:4][CH:3]=1)#[N:13]

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 122574417-Bromoisoquinoline

Product 1

HCID 20493448Isoquinoline-7-carbonitrile

Procedure

A solution of 7-bromoisoquinoline (1.80 g, 8.65 mmol) and cuprous cyanide (1.16 g, 12.97 mmol) in N-methyl pyrrolidinone (17 mL) was heated to 200° C. for 2 h. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water. The aqueous phase was back-extracted with additional ethyl acetate and the combined organic layers were washed with saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield 7-cyano-isoquinoline (770 mg): 1H NMR (300 MHz, CDCl3) δ 9.35 (s, 1H), 8.70 (d, J=5 Hz, 1H), 8.40 (s, 1H), 7.95 (d, J=8 .Hz, 1H), 7.84 (d, J=8 Hz, 1H), 7.73 (d, J=5 Hz, 1H); ESI MS m/z 155 [M+H]+.

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous phase was back-extracted with additional ethyl acetate
  3. washthe combined organic layers were washed with saturated sodium chloride
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-592bd0f48c6f4c72a5bcd096966530c9
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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