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Morpholine → Methyl 5-morpholinonicotinate

HRID 1174511
Notes
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Reaction equation

HRID 1174511 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[N:6][CH:5]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>C1(C)C=CC=CC=1.C(OCC)C.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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[N:12]1([C:8]2[CH:7]=[N:6][CH:5]=[C:4]([CH:9]=2)[C:3]([O:2][CH3:1])=[O:11])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 2

HCID 8083MorpholineHCID 699336Methyl 5-bromopyridine-3-carboxylate

Product 1

HCID 355238Methyl 5-morpholinonicotinateYield 42%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 1140
Toluene
Solvent
HCID 3283Diethyl EtherSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of methyl-5-bromonicotinate (10 g, 0.045 mol) and morpholine (4.6 g, 0.054 mol) in dry toluene (100 mL) was added fused CsCO3 (30 g, 0.09 mol) with stirring under argon. To this mixture was added BINAP (0.45 g, 0.0005 mol), Pd2(dba)3 (0.22 g, 0.00015 mol) and then the reaction mixture was refluxed at 110° C. for 50 h. The reaction mixture was cooled down to r.t. and diluted with diethyl ether (400 ml) and filtered through celite. The filtrate was concentrated under vacuum and purified by flash column chromatography (CHCl3/MeOH, 4:1) to give 4.2 g (41%) of methyl 5-morpholin-4-ylnicotinate as a liquid. TLC—Chloroform/Methanol (8/2): Rf=0.7.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled down to r.t.
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated under vacuum
  5. custompurified by flash column chromatography (CHCl3/MeOH, 4:1)

Sources & evidence

ORD record
ord-e86a4f1f9e3844ab99f10bcba60ae2eb
Source dataset
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07838522B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes