Ethanol → HCID 67207638, compound

HRID 2041715Notes

Reaction equation

HRID 2041715 reaction equation
CC([N:5]([C@H:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](Br)[CH:17]=2)[N:12]([C:20](=[O:22])[CH3:21])[C@@H:11]([CH3:23])[CH2:10]1)[C:6](=[O:8])[O-:7])(C)C.[CH3:24][N:25]([CH2:36][C:37]1[CH:42]=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=1)[C:26](=[O:35])[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C.[C:61]1([CH3:67])[CH:66]=CC=C[CH:62]=1>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:29]1([CH2:28][O:27][C:26](=[O:35])[N:25]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([C:16]3[CH:17]=[C:18]4[C:13](=[CH:14][CH:15]=3)[N:12]([C:20](=[O:22])[CH3:21])[C@@H:11]([CH3:23])[CH2:10][C@H:9]4[NH:5][C:6]([O:7][C:61]([CH3:67])([CH3:66])[CH3:62])=[O:8])=[CH:39][CH:38]=2)[CH3:24])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 5

HCID 702EthanolHCID 1140TolueneHCID 11430Potassium CarbonateHCID 67207156HCID 67207156, compoundHCID 86669445HCID 86669445, compound

Product 1

HCID 67207638HCID 67207638, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A flask was charged with 1,1-dimethylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see intermediate 50) (1 g, 2.61 mmol), phenylmethyl methyl{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}carbamate (for a preparation see intermediate 82) (1.194 g, 3.13 mmol), tetrakis(triphenylphosphine)palladium(0) (0.151 g, 0.130 mmol) and potassium carbonate (0.541 g, 3.91 mmol) then filled with ethanol (10 mL) and toluene (10 mL). The resulting mixture was degassed under house vacuo for 30 min with several quenches with nitrogen, heated to reflux for 45 min then cooled to room temperature. The insoluble material was filtered off and most of the solvent was concentrated in vacuovacuo. The residue was partitioned between DCM (100 mL) and water (100 mL). The layers were separated and the organic phase was dried through a hydrophobic frit and concentrated in vacuovacuo. Purification of the residue by SP4 using a 40 G silica cartridge (gradient:0 to 50% AcOEt in Hexanes) gave phenylmethyl({4-[(2S,4R)-1-acetyl-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate (1 g, 1.7 mmol, 69%) as a white solid.

Workup

  1. customThe resulting mixture was degassed under house vacuo for 30 min with several quenches with nitrogen
  2. temperatureheated
  3. temperatureto reflux for 45 min
  4. filtrationThe insoluble material was filtered off and most of the solvent
  5. concentrationwas concentrated in vacuovacuo
  6. customThe residue was partitioned between DCM (100 mL) and water (100 mL)
  7. customThe layers were separated
  8. customthe organic phase was dried through a hydrophobic frit
  9. concentrationconcentrated in vacuovacuo
  10. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-05e9828504854c3eaf4701b266f228cb
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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