Cesium carbonate → tert-Butyl-3-chloro-4-{[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]methyl}benzoate

HRID 536545Notes

Reaction equation

HRID 536545 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:14]3[CH2:16][CH2:15]3)[C:10](=[O:13])[NH:11][N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:23]([O:27][C:28](=[O:38])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35]Br)=[C:31]([Cl:37])[CH:30]=1)([CH3:26])([CH3:25])[CH3:24]>CC(C)=O.O>[C:23]([O:27][C:28](=[O:38])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][N:11]2[C:10](=[O:13])[N:9]([CH:14]3[CH2:16][CH2:15]3)[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[N:12]2)=[C:31]([Cl:37])[CH:30]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 19936776Tert-butyl-4-(bromomethyl)-3-chlorobenzoateHCID 580121993-(4-Chlorophenyl)-4-cyclopropyl-1H-1,2,4-triazol-5(4H)-one

Product 1

HCID 58460119tert-Butyl-3-chloro-4-{[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

An amount of 1.00 g (4.22 mmol) of 5-(4-chlorophenyl)-4-cyclopropyl-2,4-dihydro-3H-1,2,4-triazol-3-one (preparation as per WO 2007/134862 Example 36A) and 2.07 g (6.37 mmol) of caesium carbonate were suspended in 15 ml of acetone and admixed with 1.69 g (5.52 mmol) of tert-butyl-4-(bromomethyl)-3-chlorobenzoate (preparation as per WO 2003/000692, Example 4b). The mixture was stirred at 50° C. for 18 h. The suspension was diluted with water. It was extracted with twice 15 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvent on a rotary evaporator. Purification by flash chromatography over silica gel with elution with cyclohexane/ethyl acetate (gradient 9:1→3:2) gave 1.41 g (53% of theory) of the target compound in a purity of 74%.

Workup

  1. extractionIt was extracted with twice 15 ml of ethyl acetate
  2. dry with materialThe combined organic phases were dried over sodium sulphate
  3. customfreed from the solvent on a rotary evaporator
  4. customPurification by flash chromatography over silica gel
  5. washwith elution with cyclohexane/ethyl acetate (gradient 9:1→3:2)
  6. customgave 1.41 g (53% of theory) of the target compound in a purity of 74%

Sources & evidence

ORD record
ord-fac12883d60941e3a9b356802188bf9d
Source dataset
uspto-grants-2014_10
Patent number
US08859601B2

Reaction notes

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