Methyl iodide → 2-[5'-Fluoro-5-(N-[3,5-bis-(trifluoromethyl)phenyl]-N-methylamino)-3'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester

HRID 888656Notes

Reaction equation

HRID 888656 reaction equation
[CH3:1][O:2][C:3](=[O:41])[CH:4]([C:9]1[CH:10]=[C:11]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([C:37]([F:40])([F:39])[F:38])[CH:31]=2)[CH:12]=[C:13]([NH:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[CH3:42]C(C)([O-])C.[K+].CI.O1CCOCC1>CN1CCCC1=O>[CH3:1][O:2][C:3](=[O:41])[CH:4]([C:9]1[CH:10]=[C:11]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([C:37]([F:38])([F:39])[F:40])[CH:31]=2)[CH:12]=[C:13]([N:15]([C:16]2[CH:17]=[C:18]([C:26]([F:29])([F:27])[F:28])[CH:19]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:21]=2)[CH3:42])[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 312751,4-DioxaneHCID 23665647Potassium tert-butoxideHCID 577549182-[5'-Fluoro-5-(3,5-bis-trifluoromethyl-phenylamino)-3'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester

Product 1

HCID 576667032-[5'-Fluoro-5-(N-[3,5-bis-(trifluoromethyl)phenyl]-N-methylamino)-3'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl esterYield 56.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-[5′-fluoro-5-(3,5-bis-trifluoromethyl-phenylamino)-3′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester (57 mg, 0.096 mmol), potassium tert-butoxide (58 mg, 0.52 mmol), methyl iodide (60 μL, 0.11 mmol), dioxane (2 mL) and N-methylpyrrolidinone (0.2 mL) was stirred with microwave irradiation for 15 min at 130° C. The mixture was concentrated in vacuo, suspended in 1M HCl (20 mL) and extracted with diethyl ether (2×20 mL). The combined organic layer was washed with brine, dried (MgSO4), concentrated in vacuo and purified by flash column chromatography (silica, 0-5% diethyl ether in petroleum ether) to afford the title product as a colourless solid (33 mg, 56%). RT=5.24 min.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. extractionextracted with diethyl ether (2×20 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by flash column chromatography (silica, 0-5% diethyl ether in petroleum ether)

Sources & evidence

ORD record
ord-63f35ff8526d44108671d3ab7cfbe7f0
Source dataset
uspto-grants-2012_08
Patent number
US08247610B2

Reaction notes

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