Morpholine → 2-Methyl-4-morpholino-6-nitroaniline

HRID 1767017Notes

Reaction equation

HRID 1767017 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Br[C:29]1[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[C:32]([NH2:33])=[C:31]([CH3:39])[CH:30]=1.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]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].C1COCC1>[CH3:39][C:31]1[CH:30]=[C:29]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[C:32]=1[NH2:33]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 5226794-Bromo-2-methyl-6-nitroanilineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 116011322-Methyl-4-morpholino-6-nitroaniline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a 800 ml pressure flask was added Tris(dibenzylideneacetone)dipalladium (2.64 g, 2.88 mmol), 2-(Di-t-butylphosphino)biphenyl (1.42 g, 4.75 mmol) and sodium tert-butoxide (17.5 g, 182 mmol). Then dry THF (500 mL), 4-bromo-2-methyl-6-nitroaniline (30.0 g, 130 mmol) and morpholine (34 ml, 390 mmol) were added. Argon was bubbled through the solution for 1 minute and the flask was sealed. The reaction mixture was stirred at 85° C. for 3 days. THF was evaporated in vacuo and the crude product was preabsorbed on silica and this then transferred on top of a silica gel column. Elution with hexane-ethyl acetate (6:4 to 4:6 to 0:1 gradient) gave, after evaporation of solvents, the title compound (15.2 g red-brown solid, 49.3%). LCMS (M+H)+ m/z 238 (t=0.64 min.) 1H NMR (500 MHz, DMSO-d6) δ 7.32 (1H, s), 7.22 (1H, s), 6.96 (2H, s), 3.72 (4H, broad s), 2.96 (4H, broad s), 2.21 (3H, s).

Workup

  1. customArgon was bubbled through the solution for 1 minute
  2. customthe flask was sealed
  3. customTHF was evaporated in vacuo
  4. customthe crude product was preabsorbed on silica
  5. washElution with hexane-ethyl acetate (6:4 to 4:6 to 0:1 gradient)
  6. customgave
  7. customafter evaporation of solvents
  8. customLCMS (M+H)+ m/z 238 (t=0.64 min.) 1H NMR (500 MHz, DMSO-d6) δ 7.32 (1H, s), 7.22 (1H, s), 6.96 (2H, s), 3.72 (4H, broad s), 2.96 (4H, broad s), 2.21 (3H, s)

Sources & evidence

ORD record
ord-ae5192d442f747f2bf399f3868f69d6f
Source dataset
uspto-grants-2007_06
Patent number
US07232826B2

Reaction notes

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