Ethyl 4-piperidinecarboxylate → 1-(2-tert-Butoxycarbonylamino-thiazol-5-ylmethyl)-piperidine-4-carboxylic acid ethyl ester

HRID 1889185Notes

Reaction equation

HRID 1889185 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[S:9][C:10]([CH:13]=O)=[CH:11][N:12]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:16]([O:18][C:19]([CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:20])[CH3:17].C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH2:16]([O:18][C:19]([CH:21]1[CH2:26][CH2:25][N:24]([CH2:13][C:10]2[S:9][C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:15])=[N:12][CH:11]=2)[CH2:23][CH2:22]1)=[O:20])[CH3:17]

Participants

6

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 5003444Sodium cyanoborohydrideHCID 53393345tert-butyl N-(5-formyl-1,3-thiazol-2-yl)carbamate

Product 1

HCID 596100481-(2-tert-Butoxycarbonylamino-thiazol-5-ylmethyl)-piperidine-4-carboxylic acid ethyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a single necked round bottom flask (5-Formyl-thiazol-2-yl)-carbamic acid tert-butyl ester (1 g, 4.38 mmol) was dissolved in 20 ml methanol. To it piperidine-4-carboxylic acid ethyl ester (2.02 ml, 13.15 mmol) and 4-drops of glacial acetic acid was added and reaction mixture was stirred at room temperature for 2.5 hr. To it sodium cyanoborohydride (550 mg, 8.76 mmol) was added in portions and stirred for 12 hrs. Methanol was removed under reduced pressure using rotavapour. The residue was taken in water (15 ml) and ethyl acetate (25 ml), layers were separated, and aq. layer was re-extracted with ethyl acetate (25 ml). The combined organic layer was washed with brine (25 ml) and dried over anhydrous sodium sulfate. Solvent was evaporated on rotavapour, to get the yellow solid product. The crude material was purified by silica-gel column chromatography, eluting with 30-50% ethyl acetate in hexane. (0.98 g, 60% yield).

Workup

  1. customreaction mixture
  2. stirringstirred for 12 hrs
  3. customMethanol was removed under reduced pressure
  4. customethyl acetate (25 ml), layers were separated
  5. extractionaq. layer was re-extracted with ethyl acetate (25 ml)
  6. washThe combined organic layer was washed with brine (25 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customSolvent was evaporated on rotavapour
  9. customto get the yellow solid product
  10. customThe crude material was purified by silica-gel column chromatography
  11. washeluting with 30-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-69b8c252a47b46e2b1b1e5436d7df8dc
Source dataset
uspto-grants-2013_08
Patent number
US08501955B2

Reaction notes

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