Pyridine → 2-(Hydroxymethyl)-6-methylpyridine-4-carbonitrile

HRID 1908835Notes

Reaction equation

HRID 1908835 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:6]([NH2:8])=O.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl.O>[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:6]#[N:8]

Participants

6

Reactant 3

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 67027001HCID 67027001, compound

Product 1

HCID 178623062-(Hydroxymethyl)-6-methylpyridine-4-carbonitrileYield 154.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 2-hydroxymethyl-6-methyl-isonicotinamide (390 mg, 2.38 mmol) and pyridine (922 mg, 9.50 mmol) in DCM (80 mL), trifluoroacetic anhydride (1.25 g, 5.94 mmol) is added dropwise at 0° C. The mixture is stirred at rt for 1 h and becomes clear before it is carefully diluted with water and DCM. The mixture is washed twice with sat. aq. NaHCO3-solution. The washings are extracted twice with DCM. The combined org. extracts are dried over MgSO4, filtered and concentrated and briefly dried under HV to give crude 2-hydroxymethyl-6-methyl-isonicotinonitrile (544 mg, contains pyridine) as a brownish oil; LC-MS: tR=0.54 min, [M+1]+=148.99; 1H NMR (CDCl3): δ 2.66 (s, 3H), 3.48 (s br, 1H), 5.48 (s, 2H), 7.41 (s, 2H).

Workup

  1. additionis added dropwise at 0° C
  2. washThe mixture is washed twice with sat. aq. NaHCO3-solution
  3. extractionThe washings are extracted twice with DCM
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custombriefly dried under HV

Sources & evidence

ORD record
ord-ba1e6e318f0c4efaa53f8c3e855bcf9f
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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