Triethylamine → 5-(3-Trifluoromethoxy-phenyl)-pent-4-ynoic acid benzyl ester

HRID 751203Notes

Reaction equation

HRID 751203 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]([F:12])([F:11])[F:10])[CH:3]=1.[CH2:13]([O:20][C:21](=[O:26])[CH2:22][CH2:23][C:24]#[CH:25])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>C(#N)C>[CH2:13]([O:20][C:21](=[O:26])[CH2:22][CH2:23][C:24]#[C:25][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]([F:12])([F:11])[F:10])[CH:3]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 561097Benzyl 4-pentynoateHCID 27772931-Iodo-3-(trifluoromethoxy)benzene

Product 1

HCID 688239995-(3-Trifluoromethoxy-phenyl)-pent-4-ynoic acid benzyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a degassed (Ar) solution of 1-iodo-3-trifluoromethoxy-benzene (0.54 ml, 3 mmol) in acetonitrile (30 ml) was added pent-4-ynoic acid benzyl ester (719 mg, 4 mmol; A. Rosowsky, R. A. Forsch, F. S. Queener, J. Med. Chem. 2003, 46, 1726-1736), PdCl2(Ph3P)2 (122 mg, 0.17 mmol), cuprous iodide (33 mg, 0.17 mmol) and triethylamine (1.45 ml, 10 mmol). The reaction mixture was stirred for 2.5 h at ambient temperature, poured into a solution of aqueous 10% KHSO4/ice water 1/1 and extracted two times with ether. The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (silica gel, heptane/AcOEt) to give 1.13 g (3.2 mmol, 93%) of the title compound as yellow oil.

Workup

  1. extractionextracted two times with ether
  2. washThe combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue purified by flash chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-f5a6b2b3a2664502a7f101e51711f181
Source dataset
uspto-grants-2008_07
Patent number
US07405236B2

Reaction notes

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