Cesium carbonate → tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoate

HRID 83892Notes

Reaction equation

HRID 83892 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([SH:23])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25].[F:26][C:27]1[CH:28]=[C:29]([CH:37]=[C:38]([F:46])[C:39]=1[CH2:40]OS(C)(=O)=O)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].C([O-])([O-])=O.[Cs+].[Cs+]>CC#N.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:40][C:39]3[C:38]([F:46])=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:31])=[CH:28][C:27]=3[F:26])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 86662220Tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoateHCID 1784900045-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol

Product 1

HCID 66740019tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoateYield 98,450.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol (60 g, 0.16 mmol), tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoate (51 g, 0.16 mol, 1.0 eq.) and Cs2CO3 (62 g, 0.19 mol, 1.2 eq.) in MeCN (680 mL) was stirred for 2 h and evaporated to give a residue. The residue was diluted with water (1.5 L) and extracted with CH2Cl2 (1 L). The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoate (95 g, quant). 1H NMR (400 MHz, CDCl3) δ 7.40-7.42 (d, 2H), 7.19 (s, 1H), 7.14-7.16 (d, 1H), 6.76-6.80 (t, 2H), 6.51 (s, 1H), 6.41-6.49 (m, 3H), 4.07 (s, 2H), 3.75 (s, 3H), 1.58 (s, 9H), 1.47 (s, 6H).

Workup

  1. customevaporated
  2. customto give a residue
  3. extractionextracted with CH2Cl2 (1 L)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3a30401fac3845e7b3c813a9cee9d71f
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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