Benzyl chloroformate → Benzyl (4-methylpiperidin-4-yl)carbamate

HRID 1745911Notes

Reaction equation

HRID 1745911 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]([NH2:15])([CH3:14])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>O1CCOCC1.[OH-].[Na+].C(O)(C(F)(F)F)=O>[CH2:20]([O:19][C:17](=[O:18])[NH:15][C:11]1([CH3:14])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 2

HCID 10387Benzyl chloroformateHCID 11310432tert-Butyl 4-amino-4-methylpiperidine-1-carboxylate

Product 1

HCID 23282901Benzyl (4-methylpiperidin-4-yl)carbamateYield 62.9%

Reagents, catalysts & solvents 3

HCID 6422Trifluoroacetic acidSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

4-Amino-4-methyl-piperidine-1-carboxylic acid tert-butyl ester 80E (4.19 g, 19.6 mMol) was dissolved in a solution of 50 mL of dioxane and 20 mL of aqueous 2 N NaOH under an atmosphere of dry N2. To this solution was slowly added benzyl chloroformate (5.6 mL, 39 mMol) and the reaction was stirred for 3 hours at ambient temperature. The reaction mixture was concentrated under vacuum. The reaction mixture was dissolved in DCM and successively washed three with aqueous 1 N NaOH. The DCM layer was dried over Na2SO4, filtered and concentrated under vacuum to give a yellow oil. The oil was dissolved in 15 mL of TFA under an atmosphere of dry N2. The reaction mixture was concentrated under vacuum and partitioned between DCM and 0.1 N aqueous NaOH. The DCM layer was dried over Na2SO4, filtered and concentrated under vacuum to give 3.06 g of an oil. The oil was chromatographed on flash silica gel eluting with DCM to remove less polar impurities then with MeOH/DCM/NH4OH (20179.90.1) to give 2.85 g of the title compound 80F as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. dissolutionThe reaction mixture was dissolved in DCM
  3. washsuccessively washed three with aqueous 1 N NaOH
  4. dry with materialThe DCM layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give a yellow oil
  8. concentrationThe reaction mixture was concentrated under vacuum
  9. custompartitioned between DCM and 0.1 N aqueous NaOH
  10. dry with materialThe DCM layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9874a5119e144640904d0a4a24f57981
Source dataset
uspto-grants-2006_03
Patent number
US07019147B1

Reaction notes

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