Hydrochloric Acid → Methyl-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-amine

HRID 1358078Notes

Reaction equation

HRID 1358078 reaction equation
[N:1]1([C:7]2[N:12]=[CH:11][C:10]([NH2:13])=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH3:20])[CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[OH-].[Na+].[CH:30](OC)(OC)OC>FC(F)(F)C(O)=O.O1CCCC1>[CH3:30][NH:13][C:10]1[CH:11]=[N:12][C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:8][C:9]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9005Trimethyl orthoformateHCID 14798Sodium HydroxideHCID 154860516-Morpholin-4-yl-4-o-tolyl-pyridin-3-ylamineHCID 21226445Aluminium lithium hydride

Product 1

HCID 11437557Methyl-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-amineYield 66%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2.24 g (8.3 mmol) 6-morpholin-4-yl-4-o-tolyl-pyridin-3-ylamine in 17 ml trimethyl orthoformate and 3 drops trifluoroacetic acid was heated for 2 h at 130° C. The reaction mixture was evaporated and dried in vacuo for 30 min. The residual oil was dissolved in 5 ml tetrahydrofuran and was added dropwise under ice cooling to 630 mg (16.6 mmol) lithium aluminum hydride in 20 ml tetrahydrofuran. The reaction mixture was stirred for 1 h at room temperature, cooled to 0° C. again and acidified (pH 1-2) by addition of 28% hydrochloric acid solution. After stirring for 5 min, 28% sodium hydroxide solution was added to reach pH 10. The solution was filtered over celite, evaporated and purified by flash chromatography to give 1.56 g (66%) of the title compound as a white foam.

Workup

  1. customThe reaction mixture was evaporated
  2. customdried in vacuo for 30 min
  3. dissolutionThe residual oil was dissolved in 5 ml tetrahydrofuran
  4. temperaturecooled to 0° C. again
  5. stirringAfter stirring for 5 min
  6. filtrationThe solution was filtered over celite
  7. customevaporated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-bb7c624f0f7e4694b995e9f664568048
Source dataset
uspto-grants-2003_07
Patent number
US06593472B2

Reaction notes

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