Potassium Carbonate → 1-Boc-4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine

HRID 889936Notes

Reaction equation

HRID 889936 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[F:15])=[C:10]([OH:12])[CH:11]=1)([O-:5])=[O:4].[C:20]([N:27]1[CH2:32][CH2:31][CH:30]([CH2:33]OS(C)(=O)=O)[CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[OH-].[Na+]>[C:20]([N:27]1[CH2:28][CH2:29][CH:30]([CH2:33][O:12][C:10]2[C:9]([C:13]([F:18])([F:19])[C:14]([F:15])([F:16])[F:17])=[CH:8][CH:7]=[C:6]([N+:3]([O-:5])=[O:4])[CH:11]=2)[CH2:31][CH2:32]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylateHCID 17756181Phenol, 5-nitro-2-(1,1,2,2,2-pentafluoroethyl)-

Product 1

HCID 219594131-Boc-4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 14798Sodium HydroxideSolvent

Procedure

To a slurry of 60% NaH suspension in DMF (30 mL) at RT added a solution of 5-nitro-2-pentafluoroethyl-phenol (3.6 g) in 5 mL DMF. The dark red mixture was stirred at RT for 10 min then added a solution of 1-Boc-4-methylsulfonyloxymethyl-piperidine (3.1 g) in 5 mL DMF. The reaction was stirred at 60° C. and 95° C. After 1 h, added 2.94 g K2CO3 and stirred overnight at 105° C. After cooling to RT, the reaction was diluted with hexanes and 1N NaOH. Separated layers, and washed organic layer with 1N NaOH and with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification with silica gel column chromatography with 8% EtOAc/Hexanes yielded 1-Boc-4-(3-nitro-6-pentafluoroethyl-phenoxymethyl)-piperidine as a light yellow thick oil.

Workup

  1. stirringThe reaction was stirred at 60° C. and 95° C
  2. waitAfter 1 h
  3. stirringstirred overnight at 105° C
  4. temperatureAfter cooling to RT
  5. washSeparated layers, and washed organic layer with 1N NaOH
  6. dry with materialwith brine, dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification with silica gel column chromatography with 8% EtOAc/Hexanes

Sources & evidence

ORD record
ord-1efd6255992e4e52a29708f46812b516
Source dataset
uspto-grants-2006_02
Patent number
US06995162B2

Reaction notes

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