Potassium Carbonate → HCID 52934567, compound

HRID 2366955Notes

Reaction equation

HRID 2366955 reaction equation
[CH3:1][CH:2]([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)[CH3:3].Br[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][OH:40])=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>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>[C:26]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:32]3[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][OH:40])=[CH:34][CH:33]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:30])[O:4][CH:2]([CH3:1])[CH3:3])[CH2:8][C@@H:9]1[CH3:29])(=[O:28])[CH3:27]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 728512-(4-Bromophenyl)ethanolHCID 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 52934567HCID 52934567, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

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) (136. mg, 0.327 mmol), 2-(4-bromophenyl)ethanol (79 mg, 0.392 mmol), potassium carbonate (113 mg, 0.817 mmol) and tetrakis(triphenylphosphine)palladium(0) (18.87 mg, 0.016 mmol) was degassed under house vacuum for 15 min and quenched several times with nitrogen, then was then stirred at 100° C. under nitrogen for 50 min before being cooled to room temperature. Most of the solvent was removed in vacuo and the residue was partitioned between AcOEt (20 mL) and water (15 mL). The layers were separated and the aqueous phase was extracted with AcOEt (15 mL). The combined organic layers were washed with brine (15 mL), dried over MgSO4, concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 50 to 80% AcOEt in Hexanes) gave a residue which was further purified by MDAP (modifier ammonium formate) to give 1-methylethyl {(2S,4R)-1-acetyl-6-[4-(2-hydroxyethyl)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (42 mg, 0.102 mmol, 31%).

Workup

  1. customwas degassed under house vacuum for 15 min
  2. customquenched several times with nitrogen
  3. temperaturebefore being cooled to room temperature
  4. customMost of the solvent was removed in vacuo
  5. customthe residue was partitioned between AcOEt (20 mL) and water (15 mL)
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with AcOEt (15 mL)
  8. washThe combined organic layers were washed with brine (15 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash chromatography on silica gel (gradient: 50 to 80% AcOEt in Hexanes)
  12. customgave a residue which
  13. customwas further purified by MDAP (modifier ammonium formate)

Sources & evidence

ORD record
ord-01676170cc9c44869da72aff28f90dae
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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