Ethanol → HCID 86669278, compound

HRID 2366976Notes

Reaction equation

HRID 2366976 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[CH:7]([NH:15][C:16](=[O:21])[O:17][CH:18]([CH3:20])[CH3:19])[CH2:6][CH:5]1[CH3:22])(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH3:29][N:30]1[C:34]([CH3:35])=[C:33](B2OC(C)(C)C(C)(C)O2)[C:32]([CH3:45])=[N:31]1.C(O)C>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>[CH3:19][CH:18]([O:17][C:16](=[O:21])[NH:15][C@H:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:33]3[C:32]([CH3:45])=[N:31][N:30]([CH3:29])[C:34]=3[CH3:35])[CH:9]=2)[N:4]([C:1](=[O:3])[CH3:2])[C@@H:5]([CH3:22])[CH2:6]1)[CH3:20]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67197028HCID 67197028, compound

Product 1

HCID 86669278HCID 86669278, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A flask was charged with 1-methylethyl (1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (for a preparation see Example 61) (100 mg, 0.271 mmol), potassium carbonate (74.9 mg, 0.542 mmol), 1,3,5-trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (77 mg, 0.325 mmol) and tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) then filled with ethanol (1 mL) and toluene (1 mL) and the resulting mixture was refluxed under nitrogen for 18 h then cooled to room temperature and partitioned between water (40 mL) and EtOAc (40 mL). The layers were separated and the aqueous phase was extracted with EtOAc (40 mL). The combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 50% AcOEt in Hexanes) gave 1-methylethyl[(cis)-1-acetyl-2-methyl-6-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (33 mg, 0.078 mmol, 29%) as a dark yellow solid.

Workup

  1. temperaturethe resulting mixture was refluxed under nitrogen for 18 h
  2. custompartitioned between water (40 mL) and EtOAc (40 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (40 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 50% AcOEt in Hexanes)

Sources & evidence

ORD record
ord-c656f7f43d9e435b8a361cf9e36ac1f0
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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