3-Methoxypropyne → 4-Chloro-3-(3-methoxyprop-1-yn-1-yl)benzoic acid

HRID 219835Notes

Reaction equation

HRID 219835 reaction equation
[CH2:1]([O:4][CH3:5])[C:2]#[CH:3].[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1I>C1COCC1.C(N(CC)CC)C.CCOC(C)=O.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>[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[C:3]#[C:2][CH2:1][O:4][CH3:5]

Participants

7

Reactant 2

HCID 693933-MethoxypropyneHCID 27576164-Chloro-3-iodobenzoic acid

Product 1

HCID 675293394-Chloro-3-(3-methoxyprop-1-yn-1-yl)benzoic acid

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl propargyl ether (Fluka; 68898; 1.27 mL; 15 mmol; 1.50 eq.) was added dropwise to a suspension of 4-chloro-3-iodobenzoic acid (ABCR; TWC2211-D1; 2 824.60 mg; 10 mmol; 1 eq.), dichlorobis(triphenylphosphine)palladium(II) (701.91 mg; 1 mmol; 0.10 eq.) and cuprous iodide (190.45 mg; 1 mmol; 0.10 eq.) in a mixture of THF (20 mL) and triethylamine (10 mL). The reaction was stirred at RT for 2 h. The reaction mixture was quenched with saturated aqueous NH4Cl, and extracted twice with EtOAc. The combined extract were evaporated under vacuo to afford an orange solid. The latter was dissolved in EtOAc and extracted 4 times with NaOH 0.1M. Then the aqueous layer was filtered, acidified to pH=3-4 with HCl 1M, and extracted with EtOAc. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to afford the title compound as a slightly orange powder. 1H NMR (DMSO-d6, 300 MHz) δ 13.42 (br. s., 1H), 8.03 (d, J=2.07 Hz, 1H), 7.92 (dd, J=2.17, 8.38 Hz, 1H), 7.71 (d, J=8.48 Hz, 1H), 4.41 (s, 2H), 3.19-3.37 (m, 3H). LC/MS (Method B): 223.0 (M−H)−. HPLC (Method A) Rt 3.51 min (Purity: 98.8%).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  2. extractionextracted twice with EtOAc
  3. extractionThe combined extract
  4. customwere evaporated under vacuo
  5. customto afford an orange solid
  6. extractionextracted 4 times with NaOH 0.1M
  7. filtrationThen the aqueous layer was filtered
  8. extractionextracted with EtOAc
  9. dry with materialThe combined organic layers were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-5e96189b418040f68b766b12f9391724
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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