Hydrochloric Acid → tert-butyl N-[(piperidin-3-yl)methyl]carbamate

HRID 2079374Notes

Reaction equation

HRID 2079374 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:3]=1>CO.O=[Pt]=O>[NH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:13])[CH3:15])[CH2:3]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 13948280tert-Butyl (pyridin-3-ylmethyl)carbamate

Product 1

HCID 2756030tert-butyl N-[(piperidin-3-yl)methyl]carbamateYield 95%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent2×

Procedure

A cold solution of HCl in MeOH (prepared by adding acetyl chloride (13.5 mL, 14.9 g, 0.19 mol) to 1 L of MeOH) was added to a cold solution of tert-butyl pyridin-3-ylmethylcarbamate (41.0 grams, 0.20 mol) in MeOH (100 mL). The solution was transferred to a Parr hydrogenation apparatus at 12° C. PtO2 (3 g) was added, and 12 bar pressure of H2 was applied. After 16 hours 1H NMR of a concentrated sample indicated the reaction to be complete. The catalyst was filtered, and conc. aq. NaOH (20 mL) was added to neutralize the HCl. The solution was concentrated to remove the bulk of the MeOH and extracted with tert-butyl methyl ether (4×200 mL). The combined organic layers were washed with saturated aqueous NaCl solution, dried over Na2SO4, and concentrated to give the product (40.16 g, 0.187 mol, 95%) as a yellow oil that crystallized upon standing. 1H NMR (300 MHz, CDCl3): δ 4.62 (bs. s, 1H), 3.06-2.94 (m, 4H), 2.52 (dt, J=12 Hz, 3 Hz, 1H), 2.28 (dd, J=12 Hz, 10 Hz, 1H), 1.82-1.72 (m, 1H), 1.70-1.51 (m, 3H), 1.49-1.34 (m, 1H), 1.42 (s, 9H), 1.06 (dq, J=12 Hz, 4 Hz, 1H) ppm.

Workup

  1. customwas transferred to a Parr hydrogenation apparatus at 12° C
  2. customthe reaction
  3. filtrationThe catalyst was filtered
  4. additionconc. aq. NaOH (20 mL) was added
  5. concentrationThe solution was concentrated
  6. customto remove the bulk of the MeOH
  7. extractionextracted with tert-butyl methyl ether (4×200 mL)
  8. washThe combined organic layers were washed with saturated aqueous NaCl solution
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-4c5fb3bd0df44a08a2cfe4293f77d568
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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