Ethanol → HCID 86669277, compound

HRID 2366975Notes

Reaction equation

HRID 2366975 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][C:30]1[C:34](B(O)O)=[C:33]([CH3:38])[O:32][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:34]3[C:30]([CH3:29])=[N:31][O:32][C:33]=3[CH3:38])[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 27343463,5-Dimethylisoxazole-4-boronic acidHCID 67197028HCID 67197028, compound

Product 1

HCID 86669277HCID 86669277, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 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), 3,5-dimethyl-4-isoxazolylboronic acid (45.8 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 20 h. tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) was then added and the mixture refluxed for 40 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 MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 66% AcOEt in Hexanes) gave 1-methylethyl[(cis)-1-acetyl-6-(3,5-dimethyl-4-isoxazolyl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (42 mg, 0.103 mmol, 38%) as a colourless solid.

Workup

  1. additionwas then added
  2. temperaturethe mixture refluxed for 40 h
  3. custompartitioned between water (40 mL) and EtOAc (40 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (40 mL)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 66% AcOEt in Hexanes)

Sources & evidence

ORD record
ord-72ef766c90e540d38a3b6b9754605a91
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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