Trifluoroacetic acid → 3,6-Dihydro-4-[4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1(2H)-pyridinecarboxylic acid phenylmethyl ester

HRID 428737Notes

Reaction equation

HRID 428737 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH2:15][C:14](O)([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[O:25])=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O>C(Cl)Cl.C(=O)([O-])[O-].[K+].[K+]>[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:12][CH:13]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([NH:23][C:24]([O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[O:25])=[CH:21][CH:22]=3)[CH2:15][CH2:16]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 54574831HCID 54574831, compound

Product 1

HCID 542717983,6-Dihydro-4-[4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1(2H)-pyridinecarboxylic acid phenylmethyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 11430Potassium CarbonateSolvent

Procedure

A solution of 4-hydroxy-4-[4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1-piperidinecarboxylic acid phenylmethyl ester (EXAMPLE 17, Step 1, 2.50 g) in dry methylene chloride under N2 is treated with trifluoroacetic acid (0.84 mL), stirred at ambient temperature for three hours, diluted with saturated aqueous potassium carbonate (25 mL) to neutralize excess trifluouroacetic acid, and the layers are separated. The organic phase is washed with water (20 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is chromatographed on silica gel (230-400 mesh, 300 g), eluting with a gradient of ethyl acetate/hexane (20/80-50/50). Pooling of fractions with an Rf=0.69 by TLC (ethyl acetate/hexane, 50/50) and removal of solvent under reduced pressure gives the title compound, mp 146-148° C.

Workup

  1. customthe layers are separated
  2. washThe organic phase is washed with water (20 mL) and saline (20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe residue is chromatographed on silica gel (230-400 mesh, 300 g)
  6. washeluting with a gradient of ethyl acetate/hexane (20/80-50/50)
  7. customPooling of fractions with an Rf=0.69 by TLC (ethyl acetate/hexane, 50/50) and removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-e24c50f338784866924d7a99b2535472
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

Loading…