1,1'-Thiocarbonyldiimidazole → Tert-butyl 4-isothiocyanatopiperidine-1-carboxylate

HRID 30152Notes

Reaction equation

HRID 30152 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15](N1C=CN=C1)(N1C=CN=C1)=[S:16]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]=[C:15]=[S:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 802641,1'-ThiocarbonyldiimidazoleHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 58591952Tert-butyl 4-isothiocyanatopiperidine-1-carboxylateYield 94.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-15 °C

Procedure

4-Aminopiperidine-1-carboxylic acid tert-butyl ester (5.0 g, 25 mmol) (Astatech, Inc) was dissolved in dimethylformamide (120 mL) and cooled to −15° C. Thiocarbonyidiimidazole (4.8 g, 27 mmol) (Aldrich) in dimethylformamide (100 mL) was added slowly at below −10° C. The mixture was stirred at room temperature for 14 h. All solvent was removed under vacuum and the residue was dissolved in methylene chloride (200 mL) and washed 2× water. The solvent was removed and the residue was triturated with hexane. This was filtered and the solution treated with Norite and filtered through celite. Removal of solvent gave 4-isothiocyanatopiperidine-1-carboxylic acid tert-butyl ester (5.7 g, 94% yield) as oil. LR-MS-EI(+): Compatible with 242 MW.

Workup

  1. customAll solvent was removed under vacuum
  2. dissolutionthe residue was dissolved in methylene chloride (200 mL)
  3. washwashed 2× water
  4. customThe solvent was removed
  5. customthe residue was triturated with hexane
  6. filtrationThis was filtered
  7. additionthe solution treated with Norite and
  8. filtrationfiltered through celite
  9. customRemoval of solvent

Sources & evidence

ORD record
ord-403b1ef2431e46dfa0630d02c83f49f5
Source dataset
uspto-grants-2008_09
Patent number
US07423053B2

Reaction notes

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