Potassium Iodide → HCID 58294002, compound

HRID 1665244Notes

Reaction equation

HRID 1665244 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH2:11]Br)[S:9][CH:10]=1)=[O:5])[CH3:2].[F:13][C:14]1[C:19]([F:20])=[CH:18][C:17]([C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[C:16]([O:28][CH3:29])[CH:15]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH2:11][O:27][C:24]2[CH:23]=[CH:22][C:21]([C:17]3[CH:18]=[C:19]([F:20])[C:14]([F:13])=[CH:15][C:16]=3[O:28][CH3:29])=[CH:26][CH:25]=2)[S:9][CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 11043146Ethyl 2-(bromomethyl)-1,3-thiazole-4-carboxylateHCID 582599934',5'-Difluoro-2'-methoxy-biphenyl-4-ol

Product 1

HCID 58294002HCID 58294002, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-bromomethyl-thiazole-4-carboxylic acid ethyl ester (prepared according to US 2004/0266856 A1) (3.0 g, 11.99 mmol), 4′,5′-difluoro-2′-methoxy-biphenyl-4-ol (3.09 g, 13.08 mmol), potassium carbonate (6.5 g, 47.03 mmol) and potassium iodide (1.1 g, 6.626 mmol) in DMF (25 mL) was heated under microwave conditions at 130° C. for 15 min. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (3×150 mL). The organic layers were combined, washed with 1/1 water/brine (2×100 mL) and brine (100 mL), dried (MgSO4), filtered, concentrated and purified by flash chromatography (silica, 120 g, 20% to 100% ethyl acetate in hexanes) to give 2-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid ethyl ester (4.35 g, 89.5%) as an orange oil. LC-MS (ES) calculated for C20H17F2NO4S, 405.42; found m/z 406 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate (3×150 mL)
  2. washwashed with 1/1 water/brine (2×100 mL) and brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (silica, 120 g, 20% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c7e5099d2b5c4019a923801e9897b955
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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