Phenol → HCID 68008447, compound

HRID 533156Notes

Reaction equation

HRID 533156 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:17][C:18]1[C:19]([C:26]#[N:27])=[N:20][CH:21]=[C:22]([CH2:24][OH:25])[CH:23]=1.[C:28]1(O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOC(C)=O>[Cl:17][C:18]1[C:19]([C:26]#[N:27])=[N:20][CH:21]=[C:22]([CH2:24][O:25][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:23]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 58001719HCID 58001719, compound

Product 1

HCID 68008447HCID 68008447, compoundYield 80.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Di-tert-butyl azodicarboxylate (174 mg, 0.76 mmol) was added to a stirred solution of 3-chloro-5-hydroxymethyl-pyridine-2-carbonitrile (71 mg, 0.42 mmol), phenol (79 mg, 0.84 mmol) and triphenylphosphine (199 mg, 0.76 mmol) in anhydrous THF (3.3 mL) at 0° C. The mixture was stirred at 120° C. for 30 minutes under microwave irradiation. Then, the mixture was diluted with EtOAc and washed with a saturated solution of NaHCO3 and brine. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo to yield 3-chloro-5-phenoxymethyl-pyridine-2-carbonitrile (83 mg, 80%) as a white solid.

Workup

  1. washwashed with a saturated solution of NaHCO3 and brine
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; EtOAc in DCM 0/100 to 20/80)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-d2e967598e614c28803aa1abdd067576
Source dataset
uspto-grants-2014_10
Patent number
US08853237B2

Reaction notes

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