o-Toluenesulfonyl chloride → 1-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidine

HRID 1791544Notes

Reaction equation

HRID 1791544 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.N12CCN(CC1)C[CH2:17]2.[C:24]1(C)[C:25]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:27]=[CH:28][CH:29]=1>COC(C)(C)C.CCOCC>[CH3:17][C:28]1[CH:29]=[CH:24][C:25]([S:30]([O:1][CH2:2][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)(=[O:31])=[O:32])=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 8623o-Toluenesulfonyl chlorideHCID 9237DabcoHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineYield 62,906.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 15413tert-Butyl methyl etherSolvent2×

Procedure

To a solution of 4-hydroxymethyl-1-tert-butyloxycarbonylpiperidine (52.5 g, 0.244 mol) in tert-butyl methyl ether (525 ml) was added 1,4-diazabicyclo[2.2.2]octane (42.4 g, 0.378 mol). After stirring for 15 minutes at ambient temperature, the mixture was cooled to 5° C. and a solution of toluene sulphonyl chloride (62.8 g, 0.33 mmol) in tert-butyl methyl ether (525 ml) was added dropwise over 2 hours while maintaining the temperature at 0° C. After stirring for 1 hour at ambient temperature, petroleum ether (11) was added. The precipitate was removed by filtration. The filtrate was evaporated to give a solid. The solid was dissolved in ether and washed successively with 0.5M aqueous hydrochloric acid (2×500 ml), water, saturated sodium hydrogen carbonate and brine, dried (MgSO4) and evaporated to give 4-(4-methylphenylsulphonyloxymethyl)-1-tert-butyloxycarbonylpiperidine (76.7 g, 85%).

Workup

  1. temperaturethe mixture was cooled to 5° C.
  2. temperaturewhile maintaining the temperature at 0° C
  3. stirringAfter stirring for 1 hour at ambient temperature
  4. customThe precipitate was removed by filtration
  5. customThe filtrate was evaporated
  6. customto give a solid
  7. washwashed successively with 0.5M aqueous hydrochloric acid (2×500 ml), water, saturated sodium hydrogen carbonate and brine
  8. dry with materialdried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-86f4f72f75ec49408153ebc85b29e367
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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