2,6-Lutidine → N-(4-chloro-5-formylpyridin-2-yl)acetamide

HRID 1398351Notes

Reaction equation

HRID 1398351 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]=C)=[CH:6][N:5]=[C:4]([NH:10][C:11](=[O:13])[CH3:12])[CH:3]=1.N1C(C)=CC=CC=1C.I([O-])(=O)(=O)=[O:23].[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[C:7]([CH:8]=[O:23])=[CH:6][N:5]=[C:4]([NH:10][C:11](=[O:13])[CH3:12])[CH:3]=1

Participants

7

Reactant 3

HCID 79372,6-LutidineHCID 23667635Sodium periodateHCID 86695930N-(4-chloro-5-vinylpyridin-2-yl)acetamide

Product 1

HCID 86695931N-(4-chloro-5-formylpyridin-2-yl)acetamide

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of N-(4-chloro-5-vinylpyridin-2-yl)acetamide (6 g, 30.5 mmol) and 2,6-lutidine (7.11 mL, 61.0 mmol) in a mixture of 1,4-dioxane (110 mL) and water (25 mL) at 0° C. was added osmium tetroxide (2.5% in 2-methyl-2-propanol, 9.58 mL, 30.5 mmol) followed by the addition of sodium periodate (19.58 g, 92 mmol) and the reaction was stirred for 4 h. The reaction mixture was diluted with water and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate, concentrated under reduced pressure and residue so obtained was purified by comb flash column 120 g silica column using hexane/EtOAc as eluant. The desired product was isolated at 30% EtOAc in hexane. The required fractions were concentrated under reduced pressure to yield N-(4-chloro-5-formylpyridin-2-yl)acetamide as a off-white solid (5.8 g, 28.1 mmol, 92% yield). LC/MS (ESI) m/e 197.0 [(M)−, calcd for C8H6ClN2O2 197.04] LC/MS retention time (method A): tR=1.21 min; 1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H), 10.18 (s, 1H), 8.76 (s, 1H), 8.27 (s, 1H), 2.16 (s, 3H).

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined organic layers were washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure and residue
  5. customso obtained
  6. customwas purified by comb flash column 120 g silica column

Sources & evidence

ORD record
ord-05eb42ed417947439d7bfe2f097b1836
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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