Ethyl Acetate → Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate

HRID 385422Notes

Reaction equation

HRID 385422 reaction equation
[NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]([CH:14]([CH2:20][CH:21]2[CH2:23][CH2:22]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:4][C:3]=1Br.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[F-].[Cs+].CCOC(C)=O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[C:3]([C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:37])([F:36])[F:25])=[CH:28][CH:29]=2)=[CH:4][C:5]([CH:14]([CH2:20][CH:21]2[CH2:23][CH2:22]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25953Cesium fluorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57995498Ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate

Product 1

HCID 57995630Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoateYield 82%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.1, 3.3 mmol), 4-trifluoromethylphenylboronic acid (1.26 g, 6.7 mmol), CsF (1.26 g, 8.3 mmol) and Pd (PPh3)4 (0.38 g, 0.33 mmol) in 50 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 50 mL of EtOAc and 50 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.85 g, 82% yield) as a white solid.

Workup

  1. temperaturewas refluxed for 8 h under argon
  2. temperatureThe reaction mixture was cooled
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow oil
  8. customThe oil was purified by chromatography over silica gel (hexane/EtOAc)

Sources & evidence

ORD record
ord-f6a99752b8c1403d986f2e16c8152942
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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