Hydrochloric Acid → 4-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-(methyloxy)aniline

HRID 419447노트

반응식

HRID 419447 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:21][CH2:20][N:19]3[C@H:14]([CH2:15][O:16][CH2:17][CH2:18]3)[CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O.[Sn](Cl)Cl.Cl>O1CCOCC1.C1COCC1>[CH2:15]1[C@@H:14]2[CH2:13][N:12]([C:5]3[CH:6]=[CH:7][C:8]([NH2:9])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:21][CH2:20][N:19]2[CH2:18][CH2:17][O:16]1

참가 물질

6

반응물 3

HCID 313Hydrochloric Acid2회HCID 24479Stannous Chloride2회HCID 59452846(9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazine

생성물 1

HCID 594525744-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-(methyloxy)aniline수율 98%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 312751,4-Dioxane용매

실험 절차

To (9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazine (0.196 g, 0.660 mmol) in dioxane (8 mL) and THF (4 mL) cooled to 0° C. was added tin(II) chloride (0.544 g, 2.86 mmol) in HCl (2.20 mL, 37% in water, 24.6 mmol) dropwise. The reaction warmed to rt and stirred overnight. An additional amount of tin(II) chloride (1.00 g, 5.27 mmol) in HCl (4.40 mL, 37% in H2O, 49.1 mmol) was added to the reaction. When complete by TLC, the reaction was cooled to 0° C. and quenched with 6N NaOH (50 mL). The mixture was poured into H2O/EtOAc and separated. The organic layer was washed with brine and the resultant aqueous layer was back extracted with EtOAc. The combined organic layer was dried (MgSO4) and concentrated to provide the title compound of step B (0.170 g, 0.640 mmol, 98%). 1H NMR (400 MHz, DMSO-d6) b ppm 1.47 (dt, J=14.9, 6.5 Hz, 1H), 1.65-1.74 (m, 1H), 2.14-2.25 (m, 1H), 2.26-2.31 (m, 1H), 2.55-2.66 (m, 1H), 2.74 (d, J=10.8 Hz, 1H), 3.10 (t, J=10.4 Hz, 1H), 3.17 (d, J=11.5 Hz, 1H), 3.31 (d, J=11.7 Hz, 1H), 3.37 (q, J=6.2 Hz, 1H), 3.47 (td, J=11.3, 2.1 Hz, 1H), 3.60 (t, J=6.7 Hz, 1H), 3.63-3.74 (m, 4H), 4.41 (t, J=5.3 Hz, 1H), 4.46 (s, 1H), 6.23 (dd, J=8.3, 2.5 Hz, 1H), 6.42-6.50 (m, 2H).

후처리

  1. temperatureWhen complete by TLC, the reaction was cooled to 0° C.
  2. customquenched with 6N NaOH (50 mL)
  3. additionThe mixture was poured into H2O/EtOAc
  4. customseparated
  5. washThe organic layer was washed with brine
  6. extractionthe resultant aqueous layer was back extracted with EtOAc
  7. dry with materialThe combined organic layer was dried (MgSO4)
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-45eaa130ff03450aa470a54a024a8e13
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

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