5-(3-Iodophenyl)-3-methyl-1,2,4-oxadiazole → (S)-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-5-[3-(3-methyl[1,2,4]oxadiazol-5-yl)phenyl]pent-4ynoate

HRID 1637111Notes

Reaction equation

HRID 1637111 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][C@@H:5]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:9]=1)[C:6]#[CH:7].[CH3:23][C:24]1[N:28]=[C:27]([C:29]2[CH:30]=[C:31](I)[CH:32]=[CH:33][CH:34]=2)[O:26][N:25]=1>CCN(CC)CC.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>[CH3:1][O:2][C:3](=[O:22])[CH2:4][C@@H:5]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:9]=1)[C:6]#[C:7][C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([C:27]2[O:26][N:25]=[C:24]([CH3:23])[N:28]=2)[CH:30]=1

Participants

6

Reactant 2

HCID 193499795-(3-Iodophenyl)-3-methyl-1,2,4-oxadiazoleHCID 21967451(R)-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-ethynylpropionate

Product 1

HCID 21967463(S)-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-5-[3-(3-methyl[1,2,4]oxadiazol-5-yl)phenyl]pent-4ynoateYield 31.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

A solution of (R)-methyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-ethynylpropionate (150 mg, 0.5 mmol) and 3-(3-methyl[1,2,4]oxadiazol-5-yl) iodobenzene (144 mg, 0.5 mmol) in Et3N (4 ml) was treated with tetrakis(triphenylphosphine)palladium(0) (10 mg) and copper(I)iodide (10 mg). The reaction was heated to 55° for 30 min, and then the solvent was thoroughly evaporated. The residue was purified by flash chromatography (silica gel CH2Cl2 :hexane:Et2O/10:10:1) and gave the titled compound as an oil (73 mg, 17%) 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1 H), 8.02 (m, 1 H), 7.60 (m, 1 H), 7.60 (t, 1 H), 6.95 (m, 2 H), 6.86 (d, 1 H), 4.80 (m, 1 H), 4.33 (t, 1 H), 3.84 (s, 3 H), 3.72 (s, 3 H), 2.92 (d of d, 1 H), 2.82 (d of d, 1 H), 2.48 (s, 3 H), 1.78-2.02 (m, 6 H), 1.62 (m, 2 H).

Workup

  1. temperatureThe reaction was heated to 55° for 30 min
  2. customthe solvent was thoroughly evaporated
  3. customThe residue was purified by flash chromatography (silica gel CH2Cl2 :hexane:Et2O/10:10:1)

Sources & evidence

ORD record
ord-536d3aa761ef4e3294ad68bbbb063360
Source dataset
uspto-grants-2000_03
Patent number
US06037367

Reaction notes

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