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 2041695Notes

Reaction equation

HRID 2041695 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, 1.584 mmol) were mixed in DME (430 mL) and the mixture treated with a 2M Na2CO3 aqueous solution (210 mL, 420 mmol). The resulting mixture was degassed under house vacuo with several quenches with nitrogen, stirred at 105° C. under nitrogen for approximately 6 h and then cooled to room temperature and partitioned between AcOEt and water. The two layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were washed brine then were 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 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, 80.56 mmol, 76%) as a grey solid. The mother liquors were concentrated in vacuo and the residue obtained triturated with Et2O. The solid formed was filtered off to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (5.96 g, 13.64 mmol, 13%) as a grey solid.

Workup

  1. customThe resulting mixture was degassed under house vacuo with several quenches with nitrogen
  2. temperaturecooled to room temperature
  3. custompartitioned between AcOEt and water
  4. customThe two layers were separated
  5. extractionthe aqueous phase was extracted with AcOEt
  6. washThe combined organic phases were washed brine
  7. filtrationthen were 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

Sources & evidence

ORD record
ord-b2b8d2b094da440d8ca695738c468ba4
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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