Dimethylformamide → 1,1-Dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-6-cyano-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 2383308Notes

Reaction equation

HRID 2383308 reaction equation
[CH2:1]([O:5][C:6](=[O:34])[CH2:7][CH:8]1[C:17]2[C:12](=[C:13]([CH3:26])[C:14](OS(C(F)(F)F)(=O)=O)=[CH:15][CH:16]=2)[CH2:11][CH2:10][N:9]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:2][CH2:3][CH3:4].[CH3:35][N:36](C)C=O>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-]#N.[Zn+2].[C-]#N>[CH2:1]([O:5][C:6](=[O:34])[CH2:7][CH:8]1[C:17]2[C:12](=[C:13]([CH3:26])[C:14]([C:35]#[N:36])=[CH:15][CH:16]=2)[CH2:11][CH2:10][N:9]1[C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 595910841,1-Dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-5-methyl-6-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Product 1

HCID 595910861,1-Dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-6-cyano-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A solution of 1,1-dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-5-methyl-6-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 17; 837 mg, 1.64 mmol) in N,N-dimethylformamide (6 ml) was degassed under vacuum for 15 min. Tetrakis(triphenylphosphine)palladium(0) (190 mg, 0.164 mmol) and zinc cyanide (251 mg, 2.13 mmol) were then added and the resulting orange mixture stirred at 100° C. for 4 h. The mixture was cooled to room temperature and insoluble material filtered off and washed with ethyl acetate. The mother liquors were concentrated in vacuo and the residue dissolved in ethyl acetate. The solution was washed with saturated sodium bicarbonate and the aqueous phase further extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 5-25% ethyl acetate in cyclohexane, gave the title compound (600 mg) as a colourless oil.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationinsoluble material filtered off
  3. washwashed with ethyl acetate
  4. concentrationThe mother liquors were concentrated in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate
  6. washThe solution was washed with saturated sodium bicarbonate
  7. extractionthe aqueous phase further extracted twice with ethyl acetate
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography on silica gel
  12. washeluting with 5-25% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-7d0b1ee3565e498697183270d88c4c15
Source dataset
uspto-grants-2012_09
Patent number
US08263620B2

Reaction notes

Loading…