Dimethylformamide → tert-Butyl 7-cyano-1-[1-(pyridin-2-yl)cyclobutyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1850888Notes

Reaction equation

HRID 1850888 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1([CH:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18](OS(C(F)(F)F)(=O)=O)[CH:19]=3)[CH2:14][CH2:13][N:12]2[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:10][CH2:9][CH2:8]1.[CH3:36][N:37](C)C=O>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[C:36]([C:18]1[CH:19]=[C:20]2[C:15]([CH2:14][CH2:13][N:12]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH:11]2[C:7]2([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH2:10][CH2:9][CH2:8]2)=[CH:16][CH:17]=1)#[N:37]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58246194tert-Butyl 1-[1-(pyridin-2-yl)cyclobutyl]-7-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 58246239tert-Butyl 7-cyano-1-[1-(pyridin-2-yl)cyclobutyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 15826098Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

Dipalladium trisdibenzylidene acetone (0.14 g, 0.153 mmol) and diphenylphosphinoferrocene (0.338 g, 0.61 mmol) were suspended in dimethylformamide (15 ml) under an argon atmosphere. tert-Butyl 1-[1-(pyridin-2-yl)cyclobutyl]-7-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.782 g, 1.562 mmol) was added and the reaction mixture was heated to 90° C. Zinc cyanide (0.215 g, 1.831 mmol) was added over 30 min in small portions. Stirring at 90° C. was continued for 15 min. After cooling to room temperature the catalyst was removed by filtration and washed with dimethylformamide. The dimethylformamide filtrate was poured in water (200 ml). The water was extracted with dichloromethane (3×). The combined organic extracts were washed with water, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography (silica, dichloromethane, methanol). Yield: 197 mg (0.506 mmol, 33%).

Workup

  1. temperatureAfter cooling to room temperature the catalyst
  2. customwas removed by filtration
  3. washwashed with dimethylformamide
  4. additionThe dimethylformamide filtrate was poured in water (200 ml)
  5. extractionThe water was extracted with dichloromethane (3×)
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography (silica, dichloromethane, methanol)

Sources & evidence

ORD record
ord-0870a89cc3a74e2baf08733e8c6537e8
Source dataset
uspto-grants-2015_02
Patent number
US08957089B2

Reaction notes

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