4-Toluenesulfonyl chloride → Tert-butyl 4-fluoro-4-((tosyloxy)methyl)piperidine-1-carboxylate

HRID 384702Notes

Reaction equation

HRID 384702 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]1([CH2:26][OH:27])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[F:12][C:13]1([CH2:26][O:27][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 59455784Tert-butyl 4-fluoro-4-((tosyloxy)methyl)piperidine-1-carboxylateYield 80.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

p-Toluenesulfonyl chloride (230 mg, 1.209 mmol) was added portionwise to tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (188 mg, 0.806 mmol), triethylamine (227 μL, 1.612 mmol), and DMAP (9.85 mg, 0.081 mmol) in dichloromethane (2015 μL) at 0° C. The solution was stirred at room temperature overnight and then partitioned between dichloromethane and water. The organic layer was washed with 0.2M HCl and then dried (MgSO4) and concentrated. The residue was dissolved in dichloromethane and loaded onto a 25+M Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-fluoro-4-(tosyloxymethyl)piperidine-1-carboxylate (251 mg, 0.648 mmol, 80%) as a clear semi-solid.

Workup

  1. custompartitioned between dichloromethane and water
  2. washThe organic layer was washed with 0.2M HCl
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washChromatography, eluting with a gradient of EtOAc in hexanes

Sources & evidence

ORD record
ord-50706a37e1f74f7da28cb79ba6a8c24d
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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