Morpholine → 2,6-Dimethyl-4-morpholin-4-yl-phenylamine

HRID 1158671

Reaction equation

HRID 1158671 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[K+].[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1.Br[C:60]1[CH:66]=[C:65]([CH3:67])[C:63]([NH2:64])=[C:62]([CH3:68])[CH:61]=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].C1(C)C=CC=CC=1>[CH3:68][C:62]1[CH:61]=[C:60]([N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)[CH:66]=[C:65]([CH3:67])[C:63]=1[NH2:64]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 905494-Bromo-2,6-xylidineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 230094142,6-Dimethyl-4-morpholin-4-yl-phenylamineYield 41%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Procedure

Bis(dibenzylideneacetone)palladium (2.88 g) and (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.69 g) were added to dry toluene (175 mL purged with argon) and stirred for 15 minutes under argon. Potassium tert-butoxide (7.06 g), morpholine (8.7 mL) and 4-bromo-2,6-dimethylaniline (10.03 g) were added subsequently. The reaction mixture was heated to reflux for 16 hours under argon, cooled and filtered through silica (200 g). Brine (250 mL) was added and the mixture was extracted with ethyl acetate (3×200 mL). The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was dissolved in diethyl ether (250 mL), filtered through silica (200 g) and concentrated in vacuo to furnish 8.5 g (41% yield) of the title compound as a dark oil. The product was used without further purification. GC-MS (m/z) 206 (M+); tR=6.90. 1H NMR (500 MHz, CDCl3): 2.18 (s, 6H), 3.02 (m, 4H), 3.85 (m, 4H), 6.62 (b, 2H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 16 hours under argon
  3. temperaturecooled
  4. filtrationfiltered through silica (200 g)
  5. additionBrine (250 mL) was added
  6. extractionthe mixture was extracted with ethyl acetate (3×200 mL)
  7. dry with materialThe combined organic phases were dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude product was dissolved in diethyl ether (250 mL)
  10. filtrationfiltered through silica (200 g)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fe249762a237432bbca0b9750edffb22
Source dataset
uspto-grants-2010_10
Patent number
US07812023B2

Linked notes

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