Potassium Carbonate → (9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazine

HRID 419446Notes

Reaction equation

HRID 419446 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[CH:6]=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11].Cl.Cl.[CH2:15]1[C@@H:20]2[CH2:21][NH:22][CH2:23][CH2:24][N:19]2[CH2:18][CH2:17][O:16]1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:22]2[CH2:23][CH2:24][N:19]3[C@H:20]([CH2:15][O:16][CH2:17][CH2:18]3)[CH2:21]2)[CH:6]=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27792505-Fluoro-2-nitroanisoleHCID 66649934(S)-Octahydropyrazino[2,1-C][1,4]oxazine dihydrochloride

Product 1

HCID 59452846(9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazineYield 76%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Fluoro-2-nitrophenyl methyl ether (Example 22, step A) (0.318 g, 1.86 mmol), (9aS)-octahydropyrazino[2,1-c][1,4]oxazine dihydrochloride (Example 87, step G) (0.190 g, 0.880 mmol) and K2CO3 (0.614 g, 4.44 mmol) were stirred in DMSO (4 mL) at rt overnight. The reaction was diluted with EtOAc, washed with H2O (3×), dried (MgSO4) and concentrated. Purification by flash chromatography provided the title compound of step A (0.196 g, 0.660 mmol, 76%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.12-2.24 (m, 3H), 2.68 (d, J=11.4 Hz, 1H), 2.78-2.84 (m, 1H), 2.96 (td, J=12.3, 3.3 Hz, 1H), 3.10-3.18 (m, 1H), 3.52 (td, J=11.5, 2.4 Hz, 1H), 3.75 (dd, J=11.0, 2.9 Hz, 3H), 3.82-3.88 (m, 1H), 3.89 (s, 3H), 3.97 (d, J=13.9 Hz, 1H), 6.52 (d, J=2.6 Hz, 1H), 6.59 (dd, J=9.2, 2.6 Hz, 1H), 7.87 (d, J=9.5 Hz, 1H).

Workup

  1. washwashed with H2O (3×)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0ed530b9786142c4a8dc34e19752a09c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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