1-Hydroxybenzotriazole → N-methoxy-N-methylpiperidine-4-carboxamide

HRID 1619204Notes

Reaction equation

HRID 1619204 reaction equation
C(OC([N:8]1[CH2:16][CH2:15][CH:11]([C:12]([OH:14])=O)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[CH3:49][NH:50][O:51][CH3:52]>C(OCC)(=O)C.CN(C)C=O>[CH3:52][O:51][N:50]([CH3:49])[C:12]([CH:11]1[CH2:10][CH2:9][NH:8][CH2:16][CH2:15]1)=[O:14]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 22405751N-methoxy-N-methylpiperidine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-tert-butoxycarbonyl isonipecotic acid (1.50 g, 6.54 mmol, 1 eq), 1-(3-dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (1.88 g, 9.81 mmol, 1.5 eq), 1-hydroxybenzotriazole (1.33 g, 9.81 mmol, 1.5 eq), and N,N-dimethylformamide (26 ml) was treated with N,N-diisopropylethylamine (4.60 ml, 26.2 mmol, 4 eq). The resultant yellow solution was stirred at room temperature for 5 minutes, and then N,O-dimethylhydroxylamine hydrochloride (766 mg, 7.85 mmol, 1.2 eq) was added, and stirring continued for 92 hours. The reaction mixture was diluted with 100 ml of ethyl acetate and washed sequentially with 1 N aq. NaOH, 1 N aq. HCl and brine. The organic phase was dried over Na2SO4 and concentrated to give an oil which was used with no further purification.

Workup

  1. stirringstirring
  2. waitcontinued for 92 hours
  3. washwashed sequentially with 1 N aq. NaOH, 1 N aq. HCl and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. customto give an oil which
  7. customwas used with no further purification

Sources & evidence

ORD record
ord-27d9eeb982ce4d3ead793467cd59543d
Source dataset
uspto-grants-2014_07
Patent number
US08772291B2

Reaction notes

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