Trifluoroacetic acid → HCID 67235539, compound

HRID 1748288Notes

Reaction equation

HRID 1748288 reaction equation
C([O:5][C:6]([NH:8][CH2:9][C:10]([CH3:32])([CH3:31])[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:19]=2)[CH:14]=[C:13]1C(OCC)=O)=O)(C)(C)C.N1C2C(=CC=C(C(OCC)=O)C=2)C=C1C(OCC)=O.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C(O)C>[CH3:31][C:10]1([CH3:32])[CH2:11][N:12]2[C:20]3[CH:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]2[C:6](=[O:5])[NH:8][CH2:9]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 44754779Diethyl 1H-indole-2,6-dicarboxylate2×HCID 67235995HCID 67235995, compound

Product 1

HCID 67235539HCID 67235539, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of diethyl 1-{3-[(tert-butoxycarbonyl)amino-]-2,2-dimethylpropyl}-1H-indole-2,6-dicarboxylate and diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 21.9 g, 49 mmol) in CH2Cl2 (400 mL) is added TFA (100 mL). The mixture is stirred at room temperature for 2 h and then all the solvent is evaporated. The residue is dissolved in EtOAc (300 mL) and is washed with saturated NaHCO3 solution until the pH is about 7. The aqueous layer is extracted with EtOAc (100 mL) and the organic layers are combined, dried (Na2SO4) and concentrated. To a solution of the residue in ethanol (1000 mL) are added triethylamine (20.5 mL, 147 mmol) and K2CO3 (20.3 g, 147 mmol). The mixture is heated at 80° C. for 2 h and then cooled to room temperature and stirred for 16 h. The solid formed the reaction mixture is filtered off and set aside. The filtrate is concentrated and the residue is purified by flash column chromatography using methanol in CH2Cl2 to afford the title compound (7.6 g, 66% for 3 steps).

Workup

  1. customall the solvent is evaporated
  2. dissolutionThe residue is dissolved in EtOAc (300 mL)
  3. washis washed with saturated NaHCO3 solution until the pH is about 7
  4. extractionThe aqueous layer is extracted with EtOAc (100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. temperatureThe mixture is heated at 80° C. for 2 h
  8. temperaturecooled to room temperature
  9. stirringstirred for 16 h
  10. customThe solid formed the reaction mixture
  11. filtrationis filtered off
  12. concentrationThe filtrate is concentrated
  13. customthe residue is purified by flash column chromatography

Sources & evidence

ORD record
ord-4b345033657842dda424a3d849d628ab
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

Loading…