Potassium Phosphate, Tribasic → 2-(2-chloro-6-fluorobenzylthio)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-4-phenyl-1H-imidazole

HRID 1627330Notes

Reaction equation

HRID 1627330 reaction equation
Br[C:2]1[N:3]=[C:4]([S:25][CH2:26][C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:34])[N:5]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:6]=1[C:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=1)([CH3:9])[CH3:8].[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.COC1C=CC=CC=1P(C1C=CC=CC=1OC)C1C=CC=CC=1OC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:34][C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([F:33])[C:27]=1[CH2:26][S:25][C:4]1[N:5]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:6]([C:7]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)([CH3:9])[CH3:8])=[C:2]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 78464Tris(o-methoxyphenyl)phosphineHCID 866622414-bromo-2-(2-chloro-6-fluorobenzylthio)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

Product 1

HCID 667400402-(2-chloro-6-fluorobenzylthio)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-4-phenyl-1H-imidazoleYield 17.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 19096565Water ethanolSolvent

Procedure

A mixture of 4-bromo-2-(2-chloro-6-fluorobenzylthio)-5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (100 mg, 0.166 mmol), phenylboronic acid (40.5 mg, 0.332 mmol), Pd(OAc)2 (2 mg, 0.008 mmol), tris(2-methoxyphenyl)phosphine (6 mg, 0.017 mmol), and K3PO4 (106 mg, 0.498 mmol) in EtOH—H2O (3 mL, 10:1 v/v) was refluxed overnight. The reaction mixture was filtered through Celite™. The filtrate was concentrated in vacuo, dissolved in DCM (5 mL) and washed with H2O (5 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (Hex/EtOAc=9:1) to give the title product (17 mg, 17%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.23 (s, 6H), 4.57 (s, 2H), 6.10 (m, 2H), 6.30 (t, 2H), 6.50 (dd, 1H), 6.75 (m, 1H), 6.80 (d, 1H), 6.85 (dd, 1H), 7.19 (m, 1H), 7.25 (t, 2H), 7.70 (s, 1H), 7.71 (s, 1H); MS (EI) m/z 601 [M+H]+.

Workup

  1. temperaturewas refluxed overnight
  2. filtrationThe reaction mixture was filtered through Celite™
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutiondissolved in DCM (5 mL)
  5. washwashed with H2O (5 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (Hex/EtOAc=9:1)

Sources & evidence

ORD record
ord-efb42d875bbc4510aa4d9a1dbb67d81f
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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