Hydrochloric Acid → HCID 68162261, compound

HRID 2366942Notes

Reaction equation

HRID 2366942 reaction equation
CC([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)C.Br[C:32]1[N:33]=[CH:34][N:35]([CH3:37])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:44].[C:45]1(C)[CH:50]=CC=C[CH:46]=1>C(O)C.CCOCC.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>[ClH:44].[CH3:46][CH:45]([N:6]([C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:32]3[N:33]=[CH:34][N:35]([CH3:37])[CH:36]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[C:5](=[O:30])[OH:4])[CH3:50]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 11430Potassium CarbonateHCID 12776534-Bromo-1-methyl-1H-imidazoleHCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Product 1

HCID 68162261HCID 68162261, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 52) (150 mg, 0.36 mmol), 4-bromo-1-methylimidazole (0.43 mmol), tetrakis(triphenylphosphine)palladium(0) (42 mg, 10 mol %) and potassium carbonate (199 mg, 1.44 mmol) in toluene (2 mL) and ethanol (2 mL) was refluxed for 16 h then cooled to room temperature and concentrated in vacuo. The residue was partitioned between AcOEt (10 mL) and water (10 mL) and the layers were separated. The organic phase was dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) gave a residue which was treated with 1M HCl in Et2O (0.5 mL, slight excess). The solvent was evaporated and the residue triturated with Et2O to give 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(1-methyl-1H-imidazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate hydrochloride (8 mg, 0.02 mmol, 5%) as a colourless solid.

Workup

  1. customfor a preparation
  2. temperaturewas refluxed for 16 h
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between AcOEt (10 mL) and water (10 mL)
  5. customthe layers were separated
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM)
  9. customgave a residue which
  10. customThe solvent was evaporated
  11. customthe residue triturated with Et2O

Sources & evidence

ORD record
ord-94bda734960a4d7e9dd244b690bcadd3
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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