Trimethylsilyldiazomethane → Methyl 2-(5-bromopyridin-3-yl)acetate

HRID 1521603Notes

Reaction equation

HRID 1521603 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[N:6][CH:7]=1.[CH3:12][Si](C=[N+]=[N-])(C)C>C(OCC)C.CO>[CH3:12][O:10][C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 28025392-(5-Bromopyridin-3-yl)acetic acid

Product 1

HCID 23398394Methyl 2-(5-bromopyridin-3-yl)acetate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a cooled (0° C.) solution of (5-bromo-3-pyridinyl)acetic acid (1.00 g, 4.63 mmol) in diethyl ether (17 mL) and methanol (11 mL) was added a solution of (trimethylsilyl)diazomethane in diethyl ether (2.0 M, 4.6 ml, 9.3 mmol). The reaction was warmed to room temperature and then quenched by the dropwise addition of acetic acid. Once gas evolution ceased, the solution was concentrated under reduced pressure. The resulting material was diluted with ethyl acetate and washed with water and saturated aqueous sodium chloride solution. The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (20-80% ethyl acetate in hexanes) provided the title compound: LCMS m/z 231.66 [M+2+H]+; 1H NMR (500 MHz, CD3OD) δ 7.01 (s, 1H), 6.88 (s, 1H), 6.45 (s, 1H), 2.21 (s, 2H), 2.17 (s, 3H).

Workup

  1. customquenched by the dropwise addition of acetic acid
  2. concentrationthe solution was concentrated under reduced pressure
  3. additionThe resulting material was diluted with ethyl acetate
  4. washwashed with water and saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography on silica gel (20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-49f2cc182e584ccc8971aa256aeec9e5
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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