Toluene → 1-propyl-2-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4-carboxylic acid ethyl ester

HRID 250816Notes

Reaction equation

HRID 250816 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH2:14][C:15]2[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=2)[N:9]([CH2:11][CH2:12][CH3:13])[CH:10]=1)=[O:5])[CH3:2].[C:22]([N:41]1[C:45]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2B(O)O)=[N:44][N:43]=[N:42]1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=3[C:45]3[N:41]([C:22]([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:42]=[N:43][N:44]=3)=[CH:17][CH:16]=2)[N:9]([CH2:11][CH2:12][CH3:13])[CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 103427452-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acidHCID 580889072-(4-bromobenzyl)-1-propyl-1H-imidazole-4-carboxylic acid ethyl ester

Product 1

HCID 672302271-propyl-2-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4-carboxylic acid ethyl esterYield 71.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
105 °C

Procedure

2-(4-Bromobenzyl)-1-propyl-1H-imidazole-4-carboxylic acid ethyl ester (300.0 mg, 854.1 μmol) and [2-(1-trityl-1H-tetrazol-5-yl)phenyl]boronic acid (1.1 g, 2.6 mmol) were combined with 1,1′-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichlorometh (244 mg, 299 μmol), dicesium carbonate (974 mg, 3.0 mmol), toluene (11 mL, 100 mmol), and water (2.2 mL, 119.6 mmol), and stirred under nitrogen at 105° C. for 3 hours. The mixture was cooled to room temperature. Water (50 mL) was added, the mixture was extracted with EtOAc (2×50 mL), washed with saturated aqueous NaCl (50 mL), dried over MgSO4, filtered and concentrated. The product was then purified by column chromatography (0-60% EtOAc in Hexanes) to yield 1-propyl-2-[2′-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-imidazole-4-carboxylic acid ethyl ester (400 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionthe mixture was extracted with EtOAc (2×50 mL)
  3. washwashed with saturated aqueous NaCl (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was then purified by column chromatography (0-60% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-75949ffddedd41ac8304eed8ea0404fb
Source dataset
uspto-grants-2011_01
Patent number
US07863309B2

Reaction notes

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