Dimethylhydroxylamine → 4-benzyl-N-methoxy-N-methylmorpholine-2-carboxamide

HRID 30316

반응식

HRID 30316 반응식
[CH3:1][N:2](C)[OH:3].[CH3:5][Al](C)C.C(O[C:12]([CH:14]1[O:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:15]1)=[O:13])C>C(Cl)Cl>[CH3:5][O:3][N:2]([CH3:1])[C:12]([CH:14]1[O:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:15]1)=[O:13]

참가 물질

5

반응물 3

HCID 27970DimethylhydroxylamineHCID 15651196Ethyl 4-benzylmorpholine-2-carboxylateHCID 16682925Trimethylaluminum

생성물 1

HCID 597893084-benzyl-N-methoxy-N-methylmorpholine-2-carboxamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a stirred suspension of N,N-dimethylhydroxylamine (6.6 g, 67.6 mmol) in anhydrous DCM (200 mL) under nitrogen at 0° C. is added dropwise a solution of trimethylaluminium (2M solution in hexane, 34 mL, 67.6 mmol) over 30 minutes. The reaction mixture is allowed to warm up to room temperature and left stirring for 1 hour. A solution of the ester 1 (6.74 g, 27 mmol) in anhydrous DCM (100 mL) is then added dropwise over 30 minutes and the reaction mixture is left stirring overnight before quenching by cautious addition of phosphate buffer (disodium hydrogen phosphate, pH 8) solution. The precipitate is removed by filtration through a celite pad and the residue washed with chloroform. The organic phase is then concentrated in vacuo and washed with water. The aqueous layer is re-extracted with chloroform and the organic phases are combined, washed with brine, dried over magnesium sulphate and the solvent evaporated in vacuo to give 2 as a yellow oil. Alternatively, the reaction could be worked up as follows: upon addition of a solution of the ester 1 (1 eq) the reaction mixture is left stirring for 1 hour before quenching by addition of phosphate buffer (disodium hydrogen phosphate, pH 8) solution, followed by addition of water. The aqueous layer is re-extracted with DCM and the organic phases are combined, dried over magnesium sulphate and the DCM evaporated in vacuo to give 2 as a yellow oil (3.36 g, 47%). MW 264.33; C14H20N2O3; 1H NMR (CDCl3): 7.47-7.22 (5H, m), 4.55 (1H, d, 1.5 Hz), 4.00 (1H, dd, 11.5 Hz, 1.7 Hz), 3.75 (1H, dt, 11.5 Hz, 2.2 Hz), 3.65 (3H, s), 3.56 (2H, m), 3.17 (3H, s), 2.93 (1H, d, 11.3 Hz), 2.68 (1H, d, 11.3 Hz), 2.30 (2H, 11.3 Hz); LCMS: (6 min method) m/z 265 [M+H]+, RT 0.65 min.

후처리

  1. waitleft
  2. waitthe reaction mixture is left
  3. stirringstirring overnight
  4. custombefore quenching by cautious addition of phosphate buffer (disodium hydrogen phosphate, pH 8) solution
  5. customThe precipitate is removed by filtration through a celite pad
  6. washthe residue washed with chloroform
  7. concentrationThe organic phase is then concentrated in vacuo
  8. washwashed with water
  9. extractionThe aqueous layer is re-extracted with chloroform
  10. washwashed with brine
  11. dry with materialdried over magnesium sulphate
  12. customthe solvent evaporated in vacuo

출처 및 근거

ORD 기록
ord-199670b0c3c7485498b5cf0e1b79891a
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423037B2

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