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

HRID 419447ノート

反応式

HRID 419447 の反応式
[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

参加物

6

反応物 3

HCID 313Hydrochloric Acid2 回HCID 24479Stannous Chloride2 回HCID 59452846(9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazine

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-45eaa130ff03450aa470a54a024a8e13
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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