Dimethylformamide → HCID 86668527, compound

HRID 1405395Notes

Reaction equation

HRID 1405395 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][CH:5]=[C:4](I)[N:3]=1.[CH3:13][N:14](C=O)C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].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>[Cl:1][C:2]1[N:3]=[C:4]([C:13]#[N:14])[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86668526HCID 86668526, compound

Product 1

HCID 86668527HCID 86668527, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-6-iodo-3-isopropoxy-pyridine (2.00 g, 6.722 mmol) was dissolved in DMF (15 mL). Zn(CN)2 (592 mg, 5.04 mmol) was added, and the mixture was bubbled with nitrogen gas prior to the addition of Pd(PPh3)4 (600 mg, 0.519 mmol). The reaction system was sealed and heated under microwave irradiation at 100° C. for 30 minutes. The reaction mixture was diluted with EtOAc (75 mL) and washed with saturated aqueous sodium bicarbonate solution (75 mL) followed by brine (75 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain a clear oil which was purified by silica gel column chromatography: 0-30% EtOAc/hexane gradient to provide 6-chloro-5-isopropoxy-pyridine-2-carbonitrile (1.17 g, 88%) as a clear colourless oil that crystallized upon standing. ESI-MS m/z calc. 196.0, found 197.3 (M+1)+; Retention time: 1.46 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=8.4 Hz, 1H), 7.21 (d, J=8.4 Hz, 1H), 4.67 (dt, J=12.1, 6.1 Hz, 1H), 1.45 (d, J=6.1 Hz, 6H).

Workup

  1. customthe mixture was bubbled with nitrogen gas
  2. customThe reaction system was sealed
  3. washwashed with saturated aqueous sodium bicarbonate solution (75 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain a clear oil which
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e5661b05cfd9442e84a2db2dec1c5f52
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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