Formic Acid → HCID 86720834, compound

HRID 877331Notes

Reaction equation

HRID 877331 reaction equation
[C:1]1([C@H:7]([NH:65][C:66]([O:68][C@@H:69]2[CH:74]3[CH2:75][CH2:76][N:71]([CH2:72][CH2:73]3)[CH2:70]2)=[O:67])[C:8]2[CH:9]=[C:10]([CH:62]=[CH:63][CH:64]=2)[O:11][CH2:12][C:13]2[O:17][C:16]([C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][N:25]([CH2:33][C@@H:34]([C:43]3[CH:52]=[CH:51][C:50]([O:53]CC4C=CC=CC=4)=[C:49]4[C:44]=3[CH:45]=[CH:46][C:47](=[O:61])[NH:48]4)[O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:19])=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)=O>CO.CCOCC.CCOC(C)=O.[Pd]>[CH:18]([OH:20])=[O:19].[C:1]1([C@H:7]([NH:65][C:66]([O:68][C@@H:69]2[CH:74]3[CH2:75][CH2:76][N:71]([CH2:72][CH2:73]3)[CH2:70]2)=[O:67])[C:8]2[CH:9]=[C:10]([CH:62]=[CH:63][CH:64]=2)[O:11][CH2:12][C:13]2[O:17][C:16]([C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][N:25]([C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[CH2:33][C@H:34]([O:35][Si:36]([C:39]([CH3:40])([CH3:41])[CH3:42])([CH3:38])[CH3:37])[C:43]3[CH:52]=[CH:51][C:50]([OH:53])=[C:49]4[C:44]=3[CH:45]=[CH:46][C:47](=[O:61])[NH:48]4)=[O:19])=[CH:15][CH:14]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 284Formic AcidHCID 86720836HCID 86720836, compound

Product 1

HCID 86720834HCID 86720834, compoundYield 193.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 21584169Diethylether ethylacetateSolvent

Procedure

4-(((R)-2-(8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilyloxy)ethyl) (tert-butoxycarbonyl)amino)butyl 5-((3-((S)-phenyl(((R)-quinuclidin-3-yloxy)carbonylamino)methyl)phenoxy)methyl)furan-2-carboxylate (2.1 g, 1.990 mmol), 10% Pd/C (0.106 g, 0.099 mmol) and formic acid (0.092 mL, 2.388 mmol) were dissolved in MeOH (44.2 mL) and stirred at RT under balloon pressure of H2. After 2 hours reaction was complete and it was filtered on a pad of celite and the filtrate concentrated under reduced pressure to give a colourless viscous oil. The oil was dispersed in Et2O/AcOEt and evaporated 3 times in order to obtain a heavy white foam that was triturated in hexane/Et2O/AcOEt to give a white solid that was collected by filtration. The mother liquor was concentrated to give 0.44 g of a second crop of a whitish foam. The 2 crops were reunited to give 4-(tert-butoxycarbonyl((R)-2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)butyl 5-((3-((S)-phenyl(((R)-quinuclidin-3-yloxy)carbonylamino)methyl)phenoxy)-methyl)furan-2-carboxylate formate (1.95 g, 1.928 mmol, 97% yield) as white amorphous solid.

Workup

  1. customAfter 2 hours reaction
  2. filtrationit was filtered on a pad of celite
  3. concentrationthe filtrate concentrated under reduced pressure
  4. customto give a colourless viscous oil
  5. customevaporated 3 times in order
  6. customto obtain a heavy white foam that
  7. customwas triturated in hexane/Et2O/AcOEt
  8. customto give a white solid
  9. filtrationthat was collected by filtration
  10. concentrationThe mother liquor was concentrated
  11. customto give 0.44 g of a second crop of a whitish foam

Sources & evidence

ORD record
ord-703f09d87b14473f8289b8c8ada4716a
Source dataset
uspto-grants-2015_03
Patent number
US08987299B2

Reaction notes

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