Dimethylformamide → tert-Butyl 6-cyano-5-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2059935Notes

Reaction equation

HRID 2059935 reaction equation
[CH3:1][C:2]1[C:11](OS(C(F)(F)F)(=O)=O)=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:7]2.[CH3:27][N:28](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:11]1[C:2]([CH3:1])=[C:3]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:5][CH2:4]2)#[N:28]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 54756911tert-butyl 5-methyl-6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 54756912tert-Butyl 6-cyano-5-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of 1,1-dimethylethyl 5-methyl-6-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 15; 395 mg; 1.00 mmol) in DMF (4 ml) was de-gassed under high vacuum with stirring for 15 min, followed by addition of zinc cyanide (153 mg; 1.30 mmol) and tetrakis(triphenylphosphine)palladium (0) (116 mg; 0.10 mmol) under nitrogen. The resulting deep yellow mixture was stirred at 100° C. for 6 h. The solvent was removed, the residue dissolved in ethyl acetate, and the solution washed with saturated sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate, and the combined organic layers washed with brine, dried (MgSO4), and evaporated to give the crude product. Purification by flash chromatography on silica gel, eluting with a gradient of 5-25% ethyl acetate in cyclohexane, gave the title compound (214 mg) as a white solid.

Workup

  1. stirringThe resulting deep yellow mixture was stirred at 100° C. for 6 h
  2. customThe solvent was removed
  3. dissolutionthe residue dissolved in ethyl acetate
  4. washthe solution washed with saturated sodium bicarbonate
  5. extractionThe aqueous layer was further extracted with ethyl acetate
  6. washthe combined organic layers washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give the crude product
  10. customPurification by flash chromatography on silica gel
  11. washeluting with a gradient of 5-25% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-1b29d2c322254d169a80122a5dd1746f
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

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