Phosphoric Acid → 1-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidine

HRID 2401098Notes

Reaction equation

HRID 2401098 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.C(N(CC)CC)C.CN(C1C=CC=CN=1)C.[C:28]([N:35]1[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].OP(O)(O)=O>C(Cl)Cl.CN(C)C=O>[C:31]([O:30][C:28]([N:35]1[CH2:40][CH2:39][CH:38]([O:41][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:37][CH2:36]1)=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

8

Reactant 5

HCID 1004Phosphoric AcidHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 157347131-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidineYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of p-toluenesulfonylchloride (6.42 g, 33.69 mmol) in CH2Cl2 (45 mL) and N,N-dimethylformamide (5 mL), chilled to 0° C., was added triethylamine (7.2 mL, 51.66 mmol), dimethylaminopyridine (275 mg, 2.25 mmol) and then dropwise addition of N-Boc-4-hydroxypiperidine (4.52 g, 22.46 mmol) in CH2Cl2 (45 mL). The resulting mixture was stirred for 3 days and then added 1M H3PO4 (40 mL), separated the layers and extracted with CH2Cl2 (50 mL). The organic layers were combined, washed with NaHCO3 (aq) (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated to provide a crude solid which was purified by flash column chromatography (7 to 60% EtOAc/Heptane) to provide 6.21 g (78% yield) of the title compound as a solid.

Workup

  1. customseparated the layers
  2. extractionextracted with CH2Cl2 (50 mL)
  3. washwashed with NaHCO3 (aq) (40 mL), brine (40 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide a crude solid which
  8. customwas purified by flash column chromatography (7 to 60% EtOAc/Heptane)

Sources & evidence

ORD record
ord-2806d7b5e8674f029f30cc415984a337
Source dataset
uspto-grants-2014_08
Patent number
US08796278B2

Reaction notes

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