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

HRID 419447Notes

Reaction equation

HRID 419447 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-45eaa130ff03450aa470a54a024a8e13
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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