Sodium Carbonate → 3′-Chloro-2-(trifluoromethyl)[1,1′-biphenyl]-4-amine

HRID 1660937Notes

Reaction equation

HRID 1660937 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5](Br)=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>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.C1(C)C=CC=CC=1>[Cl:13][C:14]1[CH:19]=[C:18]([C:5]2[CH:4]=[CH:3][C:2]([NH2:1])=[CH:7][C:6]=2[C:8]([F:11])([F:10])[F:9])[CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 678524-Bromo-3-(trifluoromethyl)anilineHCID 2734323(3-Chlorophenyl)boronic acid

Product 1

HCID 598642013′-Chloro-2-(trifluoromethyl)[1,1′-biphenyl]-4-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 5-amino-2-bromobenzotrifluoride (Dakwood Products, Inc.) (500 mg, 2.1 mMol), 3-chlorophenylboronic acid (970 mg, 6.2 mMol, 3 equiv) (Aldrich), Pd(PPh3)4 (70 mg, 0.018 mMol, 0.03 equiv), Na2CO3 (2 M solution in H2O, 5 mL, 10 mMol, 4.76 equiv), and toluene (14 mL) is stirred at reflux for 1 h. The reaction mixture is allowed to cool to rt and filtered through a pad of celite, washing the filter cake with CH2Cl2 and H2O. The layers are separated and the aqueous phase is extracted with CH2Cl2 (2×60 mL). The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. MPLC (CH3CN/H2O/TFA) purification of the crude material affords the title compound: MS: 270.0 [M-2]−; HPLC DtRet=4.9.

Workup

  1. temperatureat reflux for 1 h
  2. filtrationfiltered through a pad of celite
  3. washwashing the filter cake with CH2Cl2 and H2O
  4. customThe layers are separated
  5. extractionthe aqueous phase is extracted with CH2Cl2 (2×60 mL)
  6. washThe combined organic phase is washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customMPLC (CH3CN/H2O/TFA) purification of the crude material

Sources & evidence

ORD record
ord-a31d34b71bb24d64a4503aefc946e2b4
Source dataset
uspto-grants-2011_10
Patent number
US08030311B2

Reaction notes

Loading…