Ammonium fluoride → Ammonia

HRID 2383388Notes

Reaction equation

HRID 2383388 reaction equation
[Si]([O:8][C@H:9]([C:47]1[CH:56]=[CH:55][C:54]([OH:57])=[C:53]2[C:48]=1[CH:49]=[CH:50][C:51](=[O:58])[NH:52]2)[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][N:28]2[CH:32]=[N:31][C:30]([C@:33]([CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)([OH:40])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[N:29]2)[CH2:23][CH2:22]1)(C(C)(C)C)(C)C.[F-].[NH4+]>CO>[NH3:11].[CH:41]1([C@@:33]([OH:40])([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:30]2[N:31]=[CH:32][N:28]([CH2:27][CH:24]3[CH2:25][CH2:26][N:21]([CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][NH:11][CH2:10][C@@H:9]([C:47]4[CH:56]=[CH:55][C:54]([OH:57])=[C:53]5[C:48]=4[CH:49]=[CH:50][C:51](=[O:58])[NH:52]5)[OH:8])[CH2:22][CH2:23]3)[N:29]=2)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

5

Reactant 2

HCID 25516Ammonium fluorideHCID 591459695-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({9-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]nonyl}amino)ethyl]-8-hydroxyquinolin-2(1H)-one

Product 2

HCID 222AmmoniaHCID 446099035-[(1R)-2-[9-[4-[[3-[(R)-cyclohexyl-hydroxy-phenylmethyl]-1,2,4-triazol-1-yl]methyl]piperidin-1-yl]nonylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

5-[(1R)-1-{[tert-buty(dimethyl)silyl]oxy}-2-({9-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperidin-1-yl]nonyl}amino)ethyl]-8-hydroxyquinolin-2(1H)-one (Preparation 8, 13.06 g, 16.06 mmol) was dissolved in methanol (430 ml) and ammonium fluoride (2.97 g, 80.3 mmol) was added. After stirring at 40° C. for 18 hours the solvent was removed in vacuo and the residue partitioned between dichloromethane/methanol (950 ml/50 ml) and saturated aqueous sodium bicarbonate solution (500 mL). The organic layer was separated and the aqueous layer further extracted with dichloromethane/methanol (450 ml/50 ml). The combined organic layers were dried over magnesium sulphate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (90:10:1, by volume) to furnish the title compound as a yellow foam, in 72.3% yield, 8.12 g.

Workup

  1. customwas removed in vacuo
  2. customthe residue partitioned between dichloromethane/methanol (950 ml/50 ml) and saturated aqueous sodium bicarbonate solution (500 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer further extracted with dichloromethane/methanol (450 ml/50 ml)
  5. dry with materialThe combined organic layers were dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-e23e8d2b7a5c4f9faa0124745264edb8
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

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