Triethylamine → HCID 68833740, compound

HRID 1986468Notes

Reaction equation

HRID 1986468 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[C:11]([CH2:30][CH:31]([CH3:33])[CH3:32])=[N:12][C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)=[CH:17][C:16](C(O)=O)=[CH:15][CH:14]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:41])C=CC=CC=1.C([N:53]([CH2:56]C)CC)C.[CH:58]1[C:70]2[CH:69]([CH2:71][OH:72])[C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[C:62]=2[CH:61]=[CH:60][CH:59]=1>O.CN(C)C=O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[C:11]([CH2:30][CH:31]([CH3:32])[CH3:33])=[N:12][C:13]2[C:18]([C:19]=1[C:20]1[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=1)=[CH:17][C:16]([NH:53][C:56](=[O:41])[O:72][CH2:71][CH:69]1[C:70]3[CH:58]=[CH:59][CH:60]=[CH:61][C:62]=3[C:63]3[C:68]1=[CH:67][CH:66]=[CH:65][CH:64]=3)=[CH:15][CH:14]=2)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 904669H-Fluorene-9-methanolHCID 199401P,P-Diphenylphosphinic azideHCID 68830056HCID 68830056, compound

Product 1

HCID 68833740HCID 68833740, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinoline-6-carboxylic acid (Example 45(1)) (2.24 g, 5.0 mmol), diphenylphosphoryl azide (1.3 ml, 6.0 mmol), triethylamine (0.84 ml, 6.0 mmol) and N,N-dimethylformamide (20 ml) was stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and toluene (30 ml) was added to the residue. The mixture was heated under reflux for 1 hr. The obtained mixture was cooled to room temperature and 9-fluorenylmethanol (1.47 g, 7.5 mmol) was added. The mixture was heated under reflux for 12 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give 9H-fluoren-9-ylmethyl 3-[[(tert-butoxycarbonyl)amino]methyl]-2-isobutyl-4-(4-methylphenyl)-6-quinolinylcarbamate (1.45 g, yield 45%) as an amorphous form.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure and toluene (30 ml)
  5. additionwas added to the residue
  6. temperatureThe mixture was heated
  7. temperatureunder reflux for 1 hr
  8. temperatureThe obtained mixture was cooled to room temperature
  9. temperatureThe mixture was heated
  10. temperatureunder reflux for 12 hrs
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e5fc05ce11eb4b9e8c5dd996e7ebe226
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

Loading…