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

HRID 1978192Notes

Reaction equation

HRID 1978192 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:5]=1[Cl:11].[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>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([C:17]#[C:16][CH2:15][N:14]([CH3:18])[CH3:13])=[CH:6][C:5]=1[Cl:11]

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 esterYield 93.6%

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

Under an atmosphere of nitrogen, a mixture of 4-bromo-2-chlorobenzoic acid methyl ester (25.13 g, 101 mmol), 1-dimethylamino-2-propyne (16 mL, 150 mmol), bis(triphenylphosphine)palladium(II) chloride (1.0 g) and copper (I) iodide (0.15 g) in 100 mL of triethylamine was heated at 60° C. for 2 hours. The cooled reaction mixture was filtered through Solka floc and the cake was washed with ethyl acetate. The filtrate was partitioned between ethyl acetate and dilute aqueous sodium thiosulfate. The organic layer was washed with water, brine and dried over sodium sulfate. The dark solution was filtered through a plug of Merck-60 silica gel and the filtrate was concentrated in vacuo to give the title compound (23.8 g) as an orange oil, which was used as such in the next step.

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through Solka floc
  3. washthe cake was washed with ethyl acetate
  4. customThe filtrate was partitioned between ethyl acetate and dilute aqueous sodium thiosulfate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationThe dark solution was filtered through a plug of Merck-60 silica gel
  8. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-1aca30fc979647a581c03f7db961e3db
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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