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

HRID 2211618Notes

Reaction equation

HRID 2211618 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 1 N NaOH. Separated layers, and washed organic layer with 1 N 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 1 N 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-878863a7c54d44bfb5a87a1df216cb6a
Source dataset
uspto-grants-2006_09
Patent number
US07101868B2

Reaction notes

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