Potassium Carbonate → HCID 66740038, compound

HRID 1627258Notes

Reaction equation

HRID 1627258 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([F:21])[C:14]=1[CH2:15]OS(C)(=O)=O)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Cl:22][C:23]1[CH:24]=[C:25]([C:30]([C:33]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[C:40]([O:45][CH3:46])[CH:39]=3)[C:36]([SH:47])=[N:35][CH:34]=2)([CH3:32])[CH3:31])[CH:26]=[CH:27][C:28]=1[Cl:29].C([O-])([O-])=O.[K+].[K+]>CC(C)=O.CCOC(C)=O.O>[Cl:22][C:23]1[CH:24]=[C:25]([C:30]([C:33]2[N:37]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[C:40]([O:45][CH3:46])[CH:39]=3)[C:36]([S:47][CH2:15][C:14]3[C:13]([F:21])=[CH:12][C:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])=[CH:3][C:2]=3[F:1])=[N:35][CH:34]=2)([CH3:32])[CH3:31])[CH:26]=[CH:27][C:28]=1[Cl:29]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 86662220Tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoateHCID 178492989HCID 178492989, compound

Product 1

HCID 66740038HCID 66740038, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl 3,5-difluoro-4-((methylsulfonyloxy)methyl)benzoate (355 mg, 1.10 mmol) and 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazole-2-thiol (402 mg, 0.98 mmol)—prepared in a manner similar to that described for Example 3 from commercially available reagents—was suspended in acetone (4 mL) and treated with K2CO3 (223 mg, 1.6 mmol). The resulting white suspension was stirred at ambient temperature. The reaction mixture rapidly became a thick slurry, and acetone (5 mL) was added to facilitate stirring. After 75 min, the reaction was diluted with EtOAc and water. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude product that was purified by flash chromatography (silica gel, EtOAc/Hex, 0:100 to 80:20) to afford the title compound (541 mg, 87% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.49-7.40 (m, 2H), 7.30-7.24 (m, 1H), 7.19 (s, 1H), 7.10 (d, J=2.2 Hz, 1H), 6.87 (ddd, J=10.7, 9.5, 5.4 Hz, 2H), 6.28 (ddd, J=8.5, 3.8, 2.5 Hz, 1H), 5.85 (dd, J=7.5, 2.4 Hz, 1H), 4.20-4.07 (m, 2H), 3.46 (s, 3H), 1.57 (s, 9H), 1.54 (s, 3H), 1.46 (s, 3H); MS (EI) m/z 637 (MH+).

Workup

  1. additionwas added
  2. stirringto facilitate stirring
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude product that
  8. customwas purified by flash chromatography (silica gel, EtOAc/Hex, 0:100 to 80:20)

Sources & evidence

ORD record
ord-fa9604d69aad40b7b1c1923ae5edbb25
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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