Toluene → (S)-2-methyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine

HRID 1431388노트

반응식

HRID 1431388 반응식
Cl[C:2]1[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:17][CH:18]1[O:23][CH2:22][CH2:21][NH:20][CH2:19]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC([O-])(C)C.[Na+].C1(C)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][C@@H:18]1[O:23][CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=2)[CH2:19]1.[CH3:17][C@H:18]1[O:23][CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=2)[CH2:19]1

참가 물질

8

반응물 5

HCID 1140TolueneHCID 4106152-MethylmorpholineHCID 23676156Sodium t-butoxideHCID 596312064-(5-Chloro-3-nitropyridin-2-yl)morpholineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

생성물 2

HCID 59631130(S)-2-methyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholineHCID 59631580(R)-2-methyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

실험 절차

A solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (2 g, 8.21 mmol; described herein), 2-methylmorpholine (996 mg, 9.85 mmol), tris(dibenzylideneacetone)dipalladium(0) (526 mg, 0.58 mmol), 2-(dicyclohexylphosphino)-2,4,6,-tri-i-propyl-1,1-biphenyl (587 mg, 1.23 mmol), sodium 2-methylpropan-2-olate (1.6 g, 16.4 mmol), and toluene (126 mL, 119 mmol) was refluxed overnight then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with satd aq. sodium bicarbonate and brine, and the organic layer dried (magnesium sulfate) and concentrated. Column chromatography and chiral separation afforded (S)-2-methyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine and (R)-2-methyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine as red solids (absolute configuration not determined and assigned randomly). Mass Spectrum (ESI) m/e=309.2 (M+1).

후처리

  1. temperaturewas refluxed overnight
  2. concentrationconcentrated
  3. washwashed with satd aq. sodium bicarbonate and brine
  4. dry with materialthe organic layer dried (magnesium sulfate)
  5. concentrationconcentrated
  6. customColumn chromatography and chiral separation

출처 및 근거

ORD 기록
ord-838e148494d5423f829681dbd6648e16
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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