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

HRID 536299Notes

Reaction equation

HRID 536299 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). Stirred the resulting mixture for 3 days and then added 1M H3PO4 (40 mL), separated the layers and extracted with CH2Cl2 (50 mL). Combined the organics, 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-f01076b99792498c80f4f3f56b6929b6
Source dataset
uspto-grants-2014_10
Patent number
US08859588B2

Reaction notes

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