Hydrochloric Acid → 8-(2-Hydroxy-pyridin-3-yl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1039010Notes

Reaction equation

HRID 1039010 reaction equation
C[O:2][C:3]1[C:8]([N:9]2[CH2:30][CH2:29][C:12]3([C:16](=[O:17])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[CH2:11][CH2:10]2)=[CH:7][CH:6]=[CH:5][N:4]=1.[Na+].[I-].C[Si](Cl)(C)C.Cl.S(=O)(O)[O-].[Na+]>C(#N)C.[Cl-].[Na+].O.CCOC(C)=O>[OH:2][C:3]1[C:8]([N:9]2[CH2:10][CH2:11][C:12]3([C:16](=[O:17])[N:15]([C:18]4[CH:19]=[CH:20][C:21]([O:24][C:25]([F:27])([F:28])[F:26])=[CH:22][CH:23]=4)[CH2:14][CH2:13]3)[CH2:29][CH2:30]2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 23665763Sodium BisulfiteHCID 56655687HCID 56655687, compound

Product 1

HCID 1785172998-(2-Hydroxy-pyridin-3-yl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 65%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 8-(2-methoxy-pyridin-3-yl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (described in example 9, 40 mg, 0.095 mmol) in acetonitrile (2 mL) at 0° C. was added NaI (28.5 mg, 0.19 mmol). TMSCl (24 uL, 0.19 mmol) was added, and the mixture was stirred and allowed to warm to rt over overnight. 1N Hydrochloric acid (1 mL), 38% aqueous sodium bisulfite solution (0.5 mL), brine and EtOAc (10 mL) were added, and the mixture was stirred for 30 min. The phases were separated, and the aqueous phase was extracted with additional EtOAc. The combined organic phases were washed with sat. NaHCO3, brine, dried (Na2SO4), filtered and evaporated under reduced pressure to yield the title compound as a light green solid (25 mg, 65%). MS (ESI): 408.3 (MH+).

Workup

  1. stirringthe mixture was stirred for 30 min
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with additional EtOAc
  4. washThe combined organic phases were washed with sat. NaHCO3, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-e031abb4cb9a4299aac34595feaa2236
Source dataset
uspto-grants-2013_10
Patent number
US08552024B2

Reaction notes

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