4-Methylmorpholine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 2200127Notes

Reaction equation

HRID 2200127 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.[C:35]([N:42]1[CH2:47][CH2:46][CH:45]([C:48]([OH:50])=O)[CH2:44][CH2:43]1)([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>CN(C=O)C.CCOC(C)=O>[CH3:5][O:4][N:3]([CH3:2])[C:48]([CH:45]1[CH2:44][CH2:43][N:42]([C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[CH2:47][CH2:46]1)=[O:50]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add N,O-dimethylhydroxylamine hydrochloride (2.52 g, 26 mmol), 1-hydroxybenzotriazole (HOBt) (2.8 g, 20.8 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl)(4 g, 20.8 mmol) and 4-methylmorpholine (5.28 g, 52 mmol) at 0° C. to the solution of N-Boc-piperidine-4-carboxylic acid (4 g, 17.4 mmol) in DMF (50 mL), stir the mixture overnight at room temperature. TLC (PE:EtOAc=1:1) shows the reaction is complete. Partition between ethyl acetate and water, collect the organic layer and wash with brine, dry over anhydrous sodium sulfate, filter and concentrate the filtrate under reduced pressure to give the crude product (4.5 g, 95%) which is used in next step without further purification.

Workup

  1. customPartition between ethyl acetate and water
  2. customcollect the organic layer
  3. washwash with brine
  4. dry with materialdry over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate the filtrate under reduced pressure

Sources & evidence

ORD record
ord-43b062700b8c48dc8a6efb6c6860a7fb
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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