Cesium carbonate → Ethyl 2-methyl-2-{2-methyl-4-[([4-(trifluoromethyl)benzyl]{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]phenoxy}propanoate

HRID 1269585Notes

Reaction equation

HRID 1269585 reaction equation
[CH3:1][C:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)=[CH:12][C:11]=1[CH3:29])([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=2)[N:32]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:8][C:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:23][CH:24]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]3[CH:42]=[CH:41][C:40]([C:43]([F:44])([F:46])[F:45])=[CH:39][CH:38]=3)[N:32]=2)=[CH:12][C:11]=1[CH3:29])([CH3:1])[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 184483252-Bromo-6-(4-(trifluoromethyl)phenyl)pyridineHCID 18448415Ethyl 2-methyl-2-[2-methyl-4-({[4-(trifluoromethyl) benzyl]amino}methyl)phenoxy]propanoate

Product 1

HCID 18448414Ethyl 2-methyl-2-{2-methyl-4-[([4-(trifluoromethyl)benzyl]{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]phenoxy}propanoateYield 45.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of ethyl 2-methyl-2-[2-methyl-4-({[4-(trifluoromethyl)benzyl]amino}methyl)phenoxy]propanoate (0.13 g, 0.318 mmol ), 2-bromo-6-[4-(trifluoromethyl) phenyl]pyridine (78.5 mg, 0.26 mmol), palladium (II) acetate (4.8 mg, 0.021 mmol), (R)-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (19.8 mg, 0.032 mmol) and caesium carbonate (0.13 g, 0.397 mmol) in toluene (1.8 mL) were heated at 70° C. in a reactivial for 18 hours. After cooling to room temperature, the reaction mixture was filtered and the solvent removed in vacuo. Purification by SPE (Silica, 10 g) eluting with 99:1–19:1 cyclohexane:EtOAc afforded the title compound as a colourless oil (75 mg).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction mixture was filtered
  3. customthe solvent removed in vacuo
  4. customPurification by SPE (Silica, 10 g)
  5. washeluting with 99:1–19:1 cyclohexane

Sources & evidence

ORD record
ord-d4bec3a271f24532b82a51b03dcfcd1f
Source dataset
uspto-grants-2007_04
Patent number
US07199239B2

Reaction notes

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