4-Methylmorpholine → N-methoxy-N-methyloxane-4-carboxamide

HRID 1045984Notes

Reaction equation

HRID 1045984 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.Cl.[CH3:11][NH:12][O:13][CH3:14].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.Cl.CCOC(C)=O>[CH3:14][O:13][N:12]([CH3:11])[C:7]([CH:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1)=[O:9]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 219302Oxane-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 23144693N-methoxy-N-methyloxane-4-carboxamideYield 81%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tetrahydro-2H-pyran-4-carboxylic acid 1 (4.0 g, 31 mmol) in DCM (65 mL) was added sequentially N,O-dimethylhydroxylamine hydrochloride (3.3 g, 34 mmol), 4-methylmorpholine (7.4 mL, 68 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.5 g, 34 mmol). The resulting mixture was stirred at RT for 18 h. At that time, the reaction was diluted with 1N HCl and EtOAc and stirred vigorously until both phases cleared. The phases were separated, and the aqueous layer was extracted with EtOAc. The organic portions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The crude residue was subjected to column chromatography (120 g silica, 80 ml/min, 0% to 100% EtOAc/hexanes) to give N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide 2 (4.3 g, 24.8 mmol, 81%). LCMS for 2 (conditions D): tR=1.12 min, m/e=174.3 (M+H, base).

Workup

  1. stirringstirred vigorously until both phases
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c72bacf6edda483d90976ee1411f9dca
Source dataset
uspto-grants-2013_10
Patent number
US08569310B2

Reaction notes

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