N,N-Diethylethanamine trihydrofluoride → Ammonia

HRID 1433298Notes

Reaction equation

HRID 1433298 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:59][Si](C(C)(C)C)(C)C)[CH2:16][NH:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35]CC4C=CC=CC=4)=[C:31]([C@@H:43]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[CH2:44][CH2:45][N:46]([CH:50]([CH3:52])[CH3:51])[CH:47]([CH3:49])[CH3:48])[CH:30]=3)=[CH:22][CH:21]=2)=[CH:11][C:10]=1[NH:67][S:68]([CH3:71])(=[O:70])=[O:69])C1C=CC=CC=1.C([O-])=O.[NH4+].F.F.F.C(N(CC)CC)C>C(O)C.CO.[OH-].[Pd+2].[OH-]>[NH3:17].[CH:50]([N:46]([CH:47]([CH3:49])[CH3:48])[CH2:45][CH2:44][C@@H:43]([C:31]1[CH:30]=[C:29]([CH2:28][CH2:27][O:26][C:23]2[CH:24]=[CH:25][C:20]([CH2:19][CH2:18][NH:17][CH2:16][C@@H:15]([C:12]3[CH:13]=[CH:14][C:9]([OH:8])=[C:10]([NH:67][S:68]([CH3:71])(=[O:70])=[O:69])[CH:11]=3)[OH:59])=[CH:21][CH:22]=2)[CH:34]=[CH:33][C:32]=1[OH:35])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([CH3:52])[CH3:51]

Participants

8

Reactant 3

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 2723923Ammonium formateHCID 57933234N-{2-(benzyloxy)-5-[(1R)-2-({2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}amino)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanesulfonamide

Product 2

HCID 222AmmoniaHCID 57933169N-{5-[(1R)-2-({2-[4-(2-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}ethoxy)phenyl]ethyl}amino)-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide

Reagents, catalysts & solvents 3

HCID 887MethanolCatalystHCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

N-{2-(benzyloxy)-5-[(1R)-2-({2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}amino)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanesulfonamide (Preparation 22, 78 mg, 0.078 mmol) was dissolved in ethanol (2 ml), ammonium formate (200 mg, 3.17 mmol) was added, heated to reflux then palladium hydroxide (20% by weight on carbon, 50 mg, 0.07 mmol) was added and after 30 minutes the reaction was cooled to room temperature and the mixture was filtered through Arbocel™ and the solvent removed in vacuo. The residue was dissolved in tetrahydrofuran (2 ml) and N,N-diethylethanamine trihydrofluoride (59 μl, 0.37 mmol) was added and after 1 drop of methanol was added and the reaction mixture was stirred over night. The solvent was removed in vacuo and the residue dissolved in 1:1 methanol/880 ammonia, the solvents removed in vacuo and this process was repeated 4 times. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (230/20/2 to 90/10/1 by volume) to furnish the title compound as a white solid, 28 mg.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. filtrationthe mixture was filtered through Arbocel™
  4. customthe solvent removed in vacuo
  5. dissolutionThe residue was dissolved in tetrahydrofuran (2 ml)
  6. customThe solvent was removed in vacuo
  7. dissolutionthe residue dissolved in 1:1 methanol/880 ammonia
  8. customthe solvents removed in vacuo
  9. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-44e964c4c92a419ea2be74d9f918c247
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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