tert-Butanol → N-(4-chloro-5-formylpyridin-2-yl)acetamide

HRID 2369530Notes

Reaction equation

HRID 2369530 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.CC([OH:26])(C)C.I([O-])(=O)(=O)=O.[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[C:7]([CH:8]=[O:26])=[CH:6][N:5]=[C:4]([NH:10][C:11](=[O:13])[CH3:12])[CH:3]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 79372,6-LutidineHCID 23667635Sodium periodateHCID 86695930N-(4-chloro-5-vinylpyridin-2-yl)acetamide

Product 1

HCID 86695931N-(4-chloro-5-formylpyridin-2-yl)acetamideYield 92.1%

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 dioxane (110 mL) and water (25 mL) at 0° C. was added osmium tetroxide, 2.5 wt % solution 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 ethyl acetate (2×100 mL). The combined organic layers were washed with brine solution, dried over sodium sulphate, concentrated under reduced pressure. The residue was purified by silica column using hexane/Ethyl acetate to yield N-(4-chloro-5-formylpyridin-2-yl)acetamide as an off-white solid (5.8 g, 28.1 mmol, 92% yield). LCMS (ESI) m/e 197.0 [(M)−, calcd for C8H6ClN2O2197.04] 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 ethyl acetate (2×100 mL)
  2. washThe combined organic layers were washed with brine solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica column

Sources & evidence

ORD record
ord-e729132a23bb49a7959839782c6275e2
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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