N-methyl-2-pyrrolidone → 2-((Tert-butyldimethylsilyloxy)methyl)isonicotinonitrile

HRID 1053784Notes

Reaction equation

HRID 1053784 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH:3]=1.[CH3:17][N:18]1C(=O)CCC1>[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>[Si:10]([O:9][CH2:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][N:5]=1)[C:17]#[N:18])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 583550294-Bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)pyridine

Product 1

HCID 583550752-((Tert-butyldimethylsilyloxy)methyl)isonicotinonitrileYield 26%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

To a stirring solution of 4-bromo-2-((tert-butyldimethylsilyloxy)methyl)pyridine INT-70 (0.800 g, 2.6 mmol) in 3 mL of 1-methy-2-pyrrolidine (NMP) was added zinc cyanide (0.610 g, 5.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.060 g, 0.052 mmol). The solution was degassed with N2 and the reaction mixture heated at 95° C. for 12 h. Upon cooling, the reaction mixture was diluted with saturated NaHCO3 and extracted with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by chromatography (MeOH/DCM) to produce 0.170 g (26%) of 2-((tert-butyldimethylsilyloxy)methyl)isonicotinonitrile INT-71 as a light yellow solid. LCMS-ESI (m/z) calculated for C13H20N2OSi: 248.4; found 249.1 [M+H]+, tR=4.21 min (Method 1).

Workup

  1. customThe solution was degassed with N2
  2. temperatureUpon cooling
  3. additionthe reaction mixture was diluted with saturated NaHCO3
  4. extractionextracted with DCM
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-be98fed5129d4267b7ab08628750fbc2
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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