Potassium Carbonate → Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-2-nitrobenzoate

HRID 1425271

Reaction equation

HRID 1425271 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)[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.ClC1[CH:36]=[CH:37][C:38]([N+:45]([O-:47])=[O:46])=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CO>[CH2:8]([O:15][C:16]([NH:18][C@H:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:36]=[CH:37][C:38]([N+:45]([O-:47])=[O:46])=[C:39]([CH:44]=2)[C:40]([O:42][CH3:43])=[O:41])[CH2:21][C@H:20]1[O:32][CH3:33])=[O:17])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 171018Methyl 5-chloro-2-nitrobenzoateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648489tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648748Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-2-nitrobenzoate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methanol (15 ml) and a 4 N hydrochloric acid/ethyl acetate solution (30 mL) were added to tert-butyl cis(±)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (40a) (1.5 g, 4.12 mmol), and the mixture was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure, azeotropically dehydrated by adding toluene, and dissolved in DMF (10 ml). Methyl 5-chloro-2-nitrobenzoate (900 mg, 4.17 mmol) and potassium carbonate (2.1 g, 15.2 mmol) were added, and the mixture was stirred at 175° C. for 24 hours. The reaction solution was diluted with ethyl acetate, washed with water, and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane) to obtain the title compound. The total resulting compound was used for the next reaction.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additionby adding toluene
  3. dissolutiondissolved in DMF (10 ml)
  4. stirringthe mixture was stirred at 175° C. for 24 hours
  5. washwashed with water
  6. concentrationconcentrated under reduced pressure
  7. customThereafter, the residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e2e2e79451c34162aaa391cb1d343dcd
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Linked notes

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