4-Methylmorpholine → Benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

HRID 2115661Notes

Reaction equation

HRID 2115661 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]([OH:19])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH3:36][NH:37][O:38][CH3:39]>C1COCC1>[CH3:39][O:38][N:37]([CH3:36])[C:17]([CH:13]1[CH2:14][CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:12]1)=[O:19]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2343391-((Benzyloxy)carbonyl)piperidine-3-carboxylic acid

Product 1

HCID 22258974Benzyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cooled (−15° C. to −20° C.) and stirred solution of 1-[(benzyloxy)carbonyl]-3-piperidinecarboxylic acid (4.0 g, 15.2 mmol) in dry THF (50 mL) including methylmorpholine (2 mL) was added dropwise a solution of isobutyl chloroformate (2.28 g, 16.7 mmol) in THF (10 mL). After the mixture was stirred at the same temperature for 20 min, a solution of N,O-dimethylhydroxylamine hydrochloride (1.63 g, 16.7 mmol) in THF (20 mL) including methylmorpholine (2 mL) was added. The reaction mixture was allowed to warm to room temperature, and then stirred for 16 hrs. The reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate and water. The separated organic phase was washed with 1N HCl, saturated NaHCO3, and brine, successively. The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to give benzyl 3-{[methoxy(methyl)amino]carbonyl}-1-piperidinecarboxylate as a colorless oil (4.7 g, yield; quant.).

Workup

  1. temperatureTo a cooled (−15° C. to −20° C.)
  2. additionwas added
  3. stirringstirred for 16 hrs
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. custompartitioned between ethyl acetate and water
  6. washThe separated organic phase was washed with 1N HCl, saturated NaHCO3, and brine
  7. dry with materialThe organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give

Sources & evidence

ORD record
ord-266896b6da504192b4eafc58d30f93b3
Source dataset
uspto-grants-2008_10
Patent number
US07435743B2

Reaction notes

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