Thionyl Chloride → Methyl alpha-phenyl-1-[4-[[[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate

HRID 1804435Notes

Reaction equation

HRID 1804435 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15](O)=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.S(Cl)(Cl)=O.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][CH:34]([CH:37]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:38]([O:40][CH3:41])=[O:39])[CH2:33][CH2:32]2)=[CH:27][CH:26]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[C:42]1([CH:37]([CH:34]2[CH2:35][CH2:36][N:31]([C:28]3[CH:27]=[CH:26][C:25]([NH:24][C:15]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:4][CH:5]=4)=[O:16])=[CH:30][CH:29]=3)[CH2:32][CH2:33]2)[C:38]([O:40][CH3:41])=[O:39])[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 552514'-(Trifluoromethyl)(1,1'-biphenyl)-2-carboxylic acidHCID 81531DiisopropylethylamineHCID 22499374(+/-)-Methyl 1-(4-aminophenyl)-alpha-phenyl-4-piperidineacetate

Product 1

HCID 22499403Methyl alpha-phenyl-1-[4-[[[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetateYield 77.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

DMF (0.5 ml) was added to a solution of 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxylic acid (0.014 mole) in DCM (50 ml) and thionyl chloride (0.028 mole). The mixture was stirred and refluxed for one hour. The solvent was evaporated. DCM (50 ml) was added twice and the solvent was evaporated. The residue was dissolved in DCM (20 ml) and this solution was added to a mixture of intermediate (15) (0.014 mole) and DIPEA (0.028 mole) in DCM (80 ml). The mixture was stirred at room temperature for three hours and washed with water. The organic layer was dried and the solvent was evaporated. The residue was crystallized from 2-propanol. The precipitate was filtered off and dried, yielding 6.2 g of methyl α-phenyl-1-[4-[[[4′-(trifluoromethyl)-[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate (melting point 151° C.) identified as compound No. 39 in the following table F-1.

Workup

  1. temperaturerefluxed for one hour
  2. customThe solvent was evaporated
  3. additionDCM (50 ml) was added twice
  4. customthe solvent was evaporated
  5. dissolutionThe residue was dissolved in DCM (20 ml)
  6. stirringThe mixture was stirred at room temperature for three hours
  7. washwashed with water
  8. customThe organic layer was dried
  9. customthe solvent was evaporated
  10. customThe residue was crystallized from 2-propanol
  11. filtrationThe precipitate was filtered off
  12. customdried

Sources & evidence

ORD record
ord-df1cbc7735294046a201f3d367f1969a
Source dataset
uspto-grants-2013_01
Patent number
US08354402B2

Reaction notes

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