Benzyl Alcohol → 8-(2-Benzyloxy-pyridine-3-sulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 2194176Notes

Reaction equation

HRID 2194176 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[C:17]([S:18]([N:21]2[CH2:42][CH2:41][C:24]3([C:28](=[O:29])[N:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=4)[CH2:26][CH2:25]3)[CH2:23][CH2:22]2)(=[O:20])=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:3]([O:10][C:12]1[C:17]([S:18]([N:21]2[CH2:22][CH2:23][C:24]3([C:28](=[O:29])[N:27]([C:30]4[CH:31]=[CH:32][C:33]([O:36][C:37]([F:38])([F:39])[F:40])=[CH:34][CH:35]=4)[CH2:26][CH2:25]3)[CH2:41][CH2:42]2)(=[O:20])=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 595779608-(2-Chloro-pyridine-3-sulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

Product 1

HCID 667872738-(2-Benzyloxy-pyridine-3-sulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (12 mg, 0.31 mmol) in DMF (2 mL) at 0° C. was added benzyl alcohol (25 uL, 0.25 mmol) and the mixture was stirred for 30 min at 0° C. A solution of 8-(2-chloro-pyridine-3-sulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (described in example 188, 100 mg, 0.20 mmol) in DMF (500 uL) was added drop-wise and the reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give the crude residue which was purified by flash column chromatography (1:2 AcOEt/heptane) which afforded the desired product as a colourless solid (100 mg, 87%). MS (ESI): 562.3 (MH+).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 16 h
  3. washwashed with brine
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude residue which
  8. customwas purified by flash column chromatography (1:2 AcOEt/heptane) which

Sources & evidence

ORD record
ord-d6f9e6e7b35847b49701834aca5fc2e4
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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