Potassium Carbonate → HCID 59458461, compound

HRID 238858Notes

Reaction equation

HRID 238858 reaction equation
C(N)(=O)C1C=CC=CC=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C@@:17]([NH:36][C:37](=[O:48])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=2)([C:25]2[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([F:35])[CH:26]=2)[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][C:12]=1[OH:49].Br[C:51]([CH3:57])([CH3:56])[C:52]([O:54][CH3:55])=[O:53].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C@:17]([C:25]2[CH:30]=[C:29]([C:31]([F:32])([F:34])[F:33])[CH:28]=[C:27]([F:35])[CH:26]=2)([NH:36][C:37](=[O:48])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:45])([F:46])[F:47])[CH:39]=2)[CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:13][C:12]=1[O:49][C:51]([CH3:57])([CH3:56])[C:52]([O:54][CH3:55])=[O:53]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 90097Methyl 2-bromo-2-methylpropionateHCID 86613064HCID 86613064, compound

Product 1

HCID 59458461HCID 59458461, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

A solution of (R)—N-(1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide benzamide, prepared as described in Example 264, (226 mg, 0.4 mmol), methyl 2-bromo-2-methylpropanoate (0.10 mL) and K2CO3 (326 mg, 2.36 mmol) in DMF (1 mL) was heated at 180° C. under microwave condition for 1200 seconds. The reaction mixture was allowed to cool, diluted with EtOAc and the organic layer was washed with H2O (2×), saturated NaCl, dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO flash chromatography (silica gel, hexanes/EtOAc) to give (R)-methyl 2-(2-fluoro-5-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(3-(trifluoromethyl)benzamido)ethyl)phenoxy)-2-methylpropanoate (Example 273, 76 mg, yield: 29%). LCMS: RT=2.26 min [M+H] 666.4 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm).

Workup

  1. temperatureto cool
  2. washthe organic layer was washed with H2O (2×), saturated NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by ISCO flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-4992a6420f984116b43154c734a5b8ea
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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