Methanol → cis(+/-)-Benzyl (1-carbamoyl-3-methoxypiperidin-4-yl)carbamate

HRID 1425077Notes

Reaction equation

HRID 1425077 reaction equation
Cl.C(OCC)(=O)C.[CH2:8]([O:15][C:16]([NH:18][C@H:19]1[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=[O:26])[CH2:21][C@H:20]1[O:32][CH3:33])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C[Si]([N:38]=C=O)(C)C.CO>C(OCC)(=O)C>[C:25]([N:22]1[CH2:23][CH2:24][C@H:19]([NH:18][C:16](=[O:17])[O:15][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@H:20]([O:32][CH3:33])[CH2:21]1)(=[O:26])[NH2:38]

Participants

6

Reactant 4

HCID 887MethanolHCID 70696Trimethylsilyl isocyanateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648489tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 131730860cis(+/-)-Benzyl (1-carbamoyl-3-methoxypiperidin-4-yl)carbamateYield 81%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 4 N hydrochloric acid/ethyl acetate solution (30 ml, 120 mmol) was added to a solution of tert-butyl cis(±)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (103a) in ethyl acetate (10 mL). The mixture was stirred for 45 minutes and the solvent was evaporated under reduced pressure. The residue was diluted with dichloromethane, washed with a 1 N aqueous sodium hydroxide solution and brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. Trimethylsilyl isocyanate (0.86 g, 7.5 mmol) was added to the resulting residue, and the mixture was stirred at room temperature for 15 hours. Methanol (1 mL) was added, followed by stirring for 30 minutes. The precipitated solid was filtered off and washed with dichloromethane to obtain 1.44 g of the title compound as a colorless solid (81%).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. additionThe residue was diluted with dichloromethane
  3. washwashed with a 1 N aqueous sodium hydroxide solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. stirringthe mixture was stirred at room temperature for 15 hours
  7. stirringby stirring for 30 minutes
  8. filtrationThe precipitated solid was filtered off
  9. washwashed with dichloromethane

Sources & evidence

ORD record
ord-6a51e8c045e344abba74c274ef904d02
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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