Benzenamine, 3,5-bis(trifluoromethyl)- → 2-[5'-Fluoro-5-(3,5-bis-trifluoromethyl-phenylamino)-3'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl ester

HRID 888655Notes

Reaction equation

HRID 888655 reaction equation
[CH3:1][O:2][C:3](=[O:34])[CH:4]([C:9]1[CH:10]=[C:11]([C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([F:33])[CH:24]=2)[CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[F:35][C:36]([F:49])([F:48])[C:37]1[CH:38]=[C:39]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[NH2:40].CC(C)([O-])C.[Na+].C(P(C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3](=[O:34])[CH:4]([C:9]1[CH:10]=[C:11]([C:23]2[CH:24]=[C:25]([F:33])[CH:26]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:28]=2)[CH:12]=[C:13]([NH:40][C:39]2[CH:41]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:43]=[C:37]([C:36]([F:35])([F:48])[F:49])[CH:38]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 23676156Sodium t-butoxideHCID 577549252-(3'-Fluoro-5-trifluoromethanesulfonyloxy-5'-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester

Product 1

HCID 577549182-[5'-Fluoro-5-(3,5-bis-trifluoromethyl-phenylamino)-3'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid methyl esterYield 47%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

A mixture of 2-(3′-fluoro-5-trifluoromethanesulfonyloxy-5′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester (48 mg, 0.10 mmol), 3,5-bis-(trifluoromethyl)aniline (18 μL, 0.12 mmol), sodium tert-butoxide (9.8 mg, 0.10 mmol), Pd(OAc)2 (2.5 mg, 0.01 mmol), 2-(di-tert-butylphosphino-1,1′-binaphthyl (3.5 mg, 0.01 mmol) and toluene (1 mL) was stirred under microwave irradiation at 130° C. for 3×10 min. The mixture was diluted with toluene (9 mL), washed with 1M HCl (2×10 mL) and brine (10 mL), dried (MgSO4), concentrated in vacuo and purified by flash column chromatography (Et2O-petroleum ether) to afford the title product as a colourless powder (28 mg, 44%). RT=4.97 min.

Workup

  1. washwashed with 1M HCl (2×10 mL) and brine (10 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. custompurified by flash column chromatography (Et2O-petroleum ether)

Sources & evidence

ORD record
ord-ff017f5eedac4bedbe83fce403f5cd9a
Source dataset
uspto-grants-2012_08
Patent number
US08247610B2

Reaction notes

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