Triphenylphosphine → 3-[1-(2-Chloro-phenyl)-ethoxy]-5-imidazol-1-yl-thiophene-2-carboxylic acid methyl ester

HRID 1930792Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH:27]([OH:29])[CH3:28].[CH3:30][O:31][C:32]([C:34]1[S:35][C:36]([N:40]2[CH:44]=[CH:43][N:42]=[CH:41]2)=[CH:37][C:38]=1O)=[O:33].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:30][O:31][C:32]([C:34]1[S:35][C:36]([N:40]2[CH:44]=[CH:43][N:42]=[CH:41]2)=[CH:37][C:38]=1[O:29][CH:27]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[Cl:20])[CH3:28])=[O:33]

Participants

Conditions

Temperature: 0 °C

Procedure

Triphenyl phosphine (304 mg, 1.16 mmol, 1.3 Eq.), 1-(2-Chloro-phenyl)-ethanol (182 mg, 1.16 mmol, 1.3 Eq.) and 3-Hydroxy-5-imidazol-1-yl-thiophene-2-carboxylic acid methyl ester (200 mg, 0.89 mmol, 1.0 Eq.) in anhydrous THF (5 mL) were cooled to 0° C. under nitrogen. Diethyl azodicarboxylate (183 μL, 1.16 mmol, 1.3 Eq.) was added dropwise. The reaction was stirred at 0° C. for 30 minutes then warmed to ambient temperature for 3.5 hours. The solvent was removed in vacuo and the residue re-dissolved in DCM and absorbed onto SiO2. The crude product wad purified by column chromatography (75% EtOAc/petroleum ether) to give the sub-title compound as a light yellow foam (290 mg, 0.80 mmol, 84%); 1H NMR (400 MHz, d-6 DMSO) δ 1.60 (3H, d), 3.80 (3H, s), 5.90 (1H, q), 7.14 (1H, d), 7.31-7.37 (1H, m), 7.43-7.49 (3H, m), 7.74-7.78 (2H, m), 8.29 (1H, d).

Workup

temperaturethen warmed to ambient temperature for 3.5 hours
customThe solvent was removed in vacuo
dissolutionthe residue re-dissolved in DCM
customabsorbed onto SiO2
customThe crude product wad purified by column chromatography (75% EtOAc/petroleum ether)

Sources & evidence

ORD record: ord-736439acb06248b48a8166ff258aba1e
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188134B2

Reaction notes

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