Sodium Carbonate → Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate

HRID 2041717Notes

Reaction equation

HRID 2041717 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].[CH2:23]([O:25][C:26]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)=[O:27])[CH3:24].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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:18]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:31]3[CH:32]=[CH:33][C:28]([C:26]([O:25][CH2:23][CH3:24])=[O:27])=[CH:29][CH:30]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5]([O:4][CH:2]([CH3:3])[CH3:1])=[O:22])[CH2:8][C@@H:9]1[CH3:21])(=[O:20])[CH3:19]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343504-Ethoxycarbonylphenylboronic acidHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 67206518Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoateYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
105 °C

Procedure

1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see intermediate 100), (39.0 g, 106 mmol), {4-[(ethyloxy)carbonyl]phenyl}boronic acid (22.5 g, 116 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.83 g, 1.58 mmol) were mixed in DME (430 mL) and the resulting mixture was treated with 2N aqueous Na2CO3 (210 mL, 420 mmol). The mixture was degassed under house vacuum with several quenches with nitrogen and then stirred at 105° C. under nitrogen for approximately 6 h before being allowed to cool to room temperature. The mixture was partitioned between AcOEt and water and the layers were separated. The aqueous phase was extracted with AcOEt and the combined organic phases were washed with brine. The organic phase was then filtered through a 70 g silica cartridge, washing the cartridge with AcOEt. The combined filtrate and washings were concentrated in vacuovacuo. The residue was triturated with Et2O then filtered off. The solid obtained was air dried to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (35.2 g, 80.2 mmol, 76%) as a grey solid. The filtrate was concentrated in vacuo and the residue obtained triturated with Et2O (approximately 30 mL). The solid formed was isolated by filtration and air dried, to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate as a grey solid (5.96 g, 13.5 mmol, 13%).

Workup

  1. customThe mixture was degassed under house vacuum with several quenches with nitrogen
  2. temperatureto cool to room temperature
  3. customThe mixture was partitioned between AcOEt and water
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with AcOEt
  6. washthe combined organic phases were washed with brine
  7. filtrationThe organic phase was then filtered through a 70 g silica cartridge
  8. washwashing the cartridge with AcOEt
  9. concentrationThe combined filtrate and washings were concentrated in vacuovacuo
  10. customThe residue was triturated with Et2O
  11. filtrationthen filtered off
  12. customThe solid obtained
  13. customdried

Sources & evidence

ORD record
ord-1478229d898d42d4b00987872572abe1
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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