Water → HCID 74763521, compound

HRID 923526Notes

Reaction equation

HRID 923526 reaction equation
C([Si](C)(C)[O:6][CH2:7][C@:8]([NH:18][C:19]([C:21]1[N:25]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH2:31][C:32]3[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=3[F:39])[C:24]2=[N:23][C:22]=1[CH3:40])=[O:20])([C:10]1[N:11]=[N:12][N:13]([CH:15]([F:17])[F:16])[N:14]=1)[CH3:9])(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.O.C(OC(C)C)(C)C>C1COCC1.C(OCC)(=O)C>[F:39][C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([F:38])[C:32]=1[CH2:31][O:30][C:29]1[C:24]2[N:25]([C:21]([C:19]([NH:18][C@@:8]([C:10]3[N:11]=[N:12][N:13]([CH:15]([F:17])[F:16])[N:14]=3)([CH3:9])[CH2:7][OH:6])=[O:20])=[C:22]([CH3:40])[N:23]=2)[CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7914Diisopropyl EtherHCID 11078149TBAF tetrahydrofuranHCID 131734994HCID 131734994, compound

Product 1

HCID 74763521HCID 74763521, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 463 mg of N-{(2R)-1-{[tert-butyl (dimethyl)silyl]oxy}-2-[2-(difluoromethyl)-2H-tetrazol-5-yl]propan-2-yl}-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide in 8 ml of THF was added 1 ml of a 1 M tetrabutylammonium fluoride/THF solution, followed by stirring at room temperature for 2 hours. To the reaction mixture was added water, followed by extraction with chloroform. The organic layer was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography. To the obtained crude product was added ethyl acetate, and diisopropyl ether was further added thereto. The mixture was stirred for 1 hour in an oil bath at 85° C., left to be cooled to room temperature, and stirred overnight. The insoluble materials were collected by filtration and the solid was washed with diisopropyl ether to obtain 260 mg of 8-[(2,6-difluorobenzyl)oxy]-N-{(2R)-2-[2-(difluoromethyl)-2H-tetrazol-5-yl]-1-hydroxypropan-2-yl}-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. extractionfollowed by extraction with chloroform
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customthe obtained residue was purified by silica gel column chromatography
  4. customTo the obtained crude product
  5. additionwas further added
  6. stirringThe mixture was stirred for 1 hour in an oil bath at 85° C.
  7. waitleft
  8. temperatureto be cooled to room temperature
  9. stirringstirred overnight
  10. filtrationThe insoluble materials were collected by filtration
  11. washthe solid was washed with diisopropyl ether

Sources & evidence

ORD record
ord-773dc30117e8443685a73d99c4052e3f
Source dataset
uspto-grants-2016_03
Patent number
US09278968B2

Reaction notes

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