N,N-Dimethylpropargylamine → 2-Chloro-4-(3-dimethylaminopropyn-1-yl)-benzoic acid methyl ester

HRID 2307367Notes

Reaction equation

HRID 2307367 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([Cl:12])[CH:3]=1.[CH3:13][N:14]([CH3:18])[CH2:15][C:16]#[CH:17]>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:12][C:4]1[CH:3]=[C:2]([C:17]#[C:16][CH2:15][N:14]([CH3:18])[CH3:13])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7]

Participants

6

Reactant 2

HCID 81643N,N-DimethylpropargylamineHCID 22058730Methyl 4-Bromo-2-chlorobenzoate

Product 1

HCID 539792842-Chloro-4-(3-dimethylaminopropyn-1-yl)-benzoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 4-bromo-2-chlorobenzoic acid, methyl ester (18.69 g) in triethylamine (110 ml), was added 1-dimethylamino-2-propyne (12.1 ml), bis(triphenylphosphine)palladium(II) chloride (1.26 g), and copper(I) iodide (0.136 g). The mixture was heated slowly to 60° C., and the temperature maintained for one hour. The reaction was cooled to room temperature, filtered through diatomaceous earth, and the collected solid washed with ethyl acetate. The solvent was removed in vacuo, the resulting residue redissolved in ethyl acetate, and washed with water (3×). The combined organic extract was dried over anhydrous sodium sulfate, and the solvent removed in vacuo to give a crude product. The crude product was purified by column chromatography on silica gel (225 g), eluting with 40% ethyl acetate/hexane. After removing the solvent in vacuo, the title compound was obtained as a viscous oil (17.7 g), MS (+FAB), m/z: 252 (M+H)+.

Workup

  1. temperaturethe temperature maintained for one hour
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through diatomaceous earth
  4. washthe collected solid washed with ethyl acetate
  5. customThe solvent was removed in vacuo
  6. dissolutionthe resulting residue redissolved in ethyl acetate
  7. washwashed with water (3×)
  8. extractionThe combined organic extract
  9. dry with materialwas dried over anhydrous sodium sulfate
  10. customthe solvent removed in vacuo
  11. customto give a crude product
  12. customThe crude product was purified by column chromatography on silica gel (225 g)
  13. washeluting with 40% ethyl acetate/hexane
  14. customAfter removing the solvent in vacuo

Sources & evidence

ORD record
ord-2ab56705216a4186a4f1f562d0b0d057
Source dataset
uspto-grants-2004_12
Patent number
US06831079B1

Reaction notes

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