3,5-Dichlorobenzylic alcohol → 3,5-Dichlorobenzyl 4-(tert-butoxycarbonylamino)piperidine-1-carboxylate

HRID 1480376Notes

Reaction equation

HRID 1480376 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([Cl:24])[CH:23]=1)[CH2:19][OH:20].[C:25](N1C=CN=C1)(N1C=CN=C1)=[O:26]>CN(C=O)C>[C:10]([O:9][C:8]([NH:7][CH:4]1[CH2:3][CH2:2][N:1]([C:25]([O:20][CH2:19][C:18]2[CH:17]=[C:16]([Cl:15])[CH:23]=[C:22]([Cl:24])[CH:21]=2)=[O:26])[CH2:6][CH2:5]1)=[O:14])([CH3:11])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 432363,5-Dichlorobenzylic alcoholHCID 682631,1'-CarbonyldiimidazoleHCID 7238334-(N-Boc-amino)piperidine

Product 1

HCID 680374753,5-Dichlorobenzyl 4-(tert-butoxycarbonylamino)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture comprising tert-butyl piperidin-4-ylcarbamate (5 g, 24.97 mmol), 3,5-dichlorobenzyl alcohol (4.42 g, 24.97 mmol) and carbonyldiimidazole (4.05 g, 24.97 mmol) in DMF (83 ml) was heated at 50° C. with stirring for 3 days. The resulting mixture was concentrated under reduced pressure. The crude material was redissolved in EtOAc and washed with 1M HCl, a saturated solution of sodium bicarbonate and brine. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The mixture was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane and then 1-10% MeOH in EtOAc to afford the title product;

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. dissolutionThe crude material was redissolved in EtOAc
  3. washwashed with 1M HCl
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe mixture was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-e6657b4101ba4f178cb1892840eb6a5b
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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