Cesium carbonate → HCID 67049941, compound

HRID 1875724Notes

Reaction equation

HRID 1875724 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][OH:11])=[CH:6][CH:5]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[C:60]1[C:65]([C:66]2[N:70]([CH2:71][CH:72]3[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]3)[C:69]3[CH:78]=[C:79]([F:83])[C:80]([F:82])=[CH:81][C:68]=3[N:67]=2)=[CH:64][CH:63]=[CH:62][N:61]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][C:60]2[C:65]([C:66]3[N:70]([CH2:71][CH:72]4[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77]4)[C:69]4[CH:78]=[C:79]([F:83])[C:80]([F:82])=[CH:81][C:68]=4[N:67]=3)=[CH:64][CH:63]=[CH:62][N:61]=2)=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 81325Methyl 4-(hydroxymethyl)benzoateHCID 634876Binap, (A+-)-HCID 866522862-(2-chloro-pyridin-3-yl)-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazole

Product 1

HCID 67049941HCID 67049941, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

A solution of 4-hydroxymethyl-benzoic acid methyl ester (0.14 g, 0.84 mmol; CAS Reg. No. 6908-41-4), palladium (II) acetate (19 mg, 0.084 mmol; CAS Reg. No.) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (52 mg, 0.084 mmol; CAS Reg. No.) in dry toluene (10 ml) was stirred at 25° C. for 5 min. under argon atmosphere. To the resulting deep red solution was then added a solution of 2-(2-chloro-pyridin-3-yl)-1-cyclohexylmethyl-5,6-difluoro-1H-benzoimidazole (Ex. 1, intermediate a, 0.30 g, 0.84 mmol) in toluene (5 ml) and cesium carbonate (0.82 g, 2.52 mmol). The flask was purged with argon, and the reaction mixture was heated at 100° C. for 12 h. The solid was filtered, the filtrate concentrated in vacuo and the residue was purified by column chromatography over silica gel (15-20% ethyl acetate/n-hexane) to afford the title compound as brown sticky solid (60%). MS (Turbo Spray): m/z=492.3 (M+H).

Workup

  1. customThe flask was purged with argon
  2. filtrationThe solid was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customthe residue was purified by column chromatography over silica gel (15-20% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-fd8237dfa1b94e47b0bc897d1f409119
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

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