Methanol → 3-(Prop-1-ynyl)-4-propylbenzoic acid

HRID 710408Notes

Reaction equation

HRID 710408 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH2:11][CH2:12][CH3:13])[C:5]([OH:7])=[O:6].S1(C2[C:20](=[CH:21]C=CC=2)[C:18](=O)N1)(=O)=O.C([Mg]Br)#CC.CO>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:18]([C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH2:11][CH2:12][CH3:13])[C:5]([OH:7])=[O:6])#[C:20][CH3:21]

Participants

9

Reactant 4

HCID 887MethanolHCID 5143SaccharinHCID 448288293-Iodo-4-propylbenzoic acid2×HCID 178419101HCID 178419101, compound

Product 1

HCID 667267763-(Prop-1-ynyl)-4-propylbenzoic acidYield 172.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of the product of Step A (0.36 g; 1.24 mmol) in HMDSA (2 ml) and saccharine (0.1 g) was refluxed under N2 until reaction became homogenous (˜30 min). After cooling to room temperature, the HMDSA was removed in vacuo and the residue was diluted to 4 ml with anhydrous THF. At the same time ZnCl2 (0.2 g; 1.47 mmol) was heated to ˜120° C., in separate flask, in vacuo, cooled to room temperature under N2 and diluted to 4 ml with anhydrous THF. To it 0.5 M prop-1-ynyl-magnesium bromide in THF (4.9 ml; 2.45 mmol) was added at room temperature and this was stirred for 10 min under N2. To it a solution of the protected product of Step A was added, followed by Pd(PPh3)4 (0.11 g; 0.095 mmol) and CuI (0.05 g; 0.26 mmol). After stirring for 1 h at room temperature under N2, MeOH (5 ml) was added and solvents were removed under reduced pressure. The residue was suspended in H2O (5 ml) and pH was adjusted to ˜10 with diluted NaOH. The insoluble material was removed by filtration and filtrate acidified to ˜3 with diluted HCl. The product was taken up by (2×10 ml). The organic phase was dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness under reduced pressure to give the title compound (0.19 g; 76%), as creamy solid. 1H-NMR (CDCl3) 0.91-0.99 (m, 3H); 1.6-1.74 (m, 2H); 2.09 (s, 3H); 2.7-2.81 (m, 2H); 7.2-7.27 (m, 1H+CDCl3); 7.8-7.92 (m, 1H); 8.52 (m, 1H).

Workup

  1. temperaturewas refluxed under N2 until reaction
  2. custom(˜30 min)
  3. customthe HMDSA was removed in vacuo
  4. additionthe residue was diluted to 4 ml with anhydrous THF
  5. temperaturecooled to room temperature under N2
  6. stirringAfter stirring for 1 h at room temperature under N2
  7. customsolvents were removed under reduced pressure
  8. customThe insoluble material was removed by filtration and filtrate
  9. dry with materialThe organic phase was dried over anhydrous MgSO4
  10. filtrationfiltered
  11. customfiltrate evaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-e0085343bba64f94bc2a2ad465e51a22
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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