Dimethylformamide → 2-(azidomethyl)-4-chloro-N-methylbenzamide

HRID 2252818Notes

Reaction equation

HRID 2252818 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[C:4]([CH2:12]O)[CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.CN(C=O)C.[N:31]([Si](C)(C)C)=[N+:32]=[N-:33]>C(Cl)Cl.C(Cl)(Cl)Cl>[N:31]([CH2:12][C:4]1[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:5]=1[C:6]([NH:8][CH3:9])=[O:7])=[N+:32]=[N-:33]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 78378AzidotrimethylsilaneHCID 691802354-chloro-2-(hydroxymethyl)-N-methylbenzamide

Product 1

HCID 866001792-(azidomethyl)-4-chloro-N-methylbenzamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 4-chloro-2-(hydroxymethyl)-N-methylbenzamide (5.81 g, 29.2 mmol) in methylene chloride (200 mL) cooled in an ice bath, was added triethylamine (5.10 mL, 36.6 mmol) and methanesulfonyl chloride (2.50 mL, 32.3 mmol). After 90 min, the reaction was diluted with chloroform and partitioned with aqueous sodium bicarbonate and brine. After extracting three times with chloroform, the combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. To this residue was added DMF (50 mL) sodium azide (0.35 g, 5.4 mmol) and azidotrimethylsilane (2.6 mL, 19.6 mmol) portionwise with stirring at 40° C. for three days. The reaction was concentrated in vacuo and partitioned between chloroform and aqueous sodium bicarbonate. After extracting three times with chloroform, the combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography eluting with a 30-50% ethyl acetate/hexane gradient. Fractions were concentrated in vacuo to afford 2-(azidomethyl)-4-chloro-N-methylbenzamide.

Workup

  1. custompartitioned with aqueous sodium bicarbonate and brine
  2. extractionAfter extracting three times with chloroform
  3. dry with materialthe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. concentrationThe reaction was concentrated in vacuo
  7. custompartitioned between chloroform and aqueous sodium bicarbonate
  8. extractionAfter extracting three times with chloroform
  9. dry with materialthe combined organics were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography
  13. washeluting with a 30-50% ethyl acetate/hexane gradient
  14. concentrationFractions were concentrated in vacuo

Sources & evidence

ORD record
ord-35e9771442d54cb7824b642a2fedfc16
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

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