Morpholine → 2-Methoxy-4-methyl-6-morpholino-pyridine-3-carboxylic acid methylester

HRID 1753877Notes

Reaction equation

HRID 1753877 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([O:13][CH3:14])=[N:7][C:8](Cl)=[CH:9][C:10]=1[CH3:11])=[O:4].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.CCN(CC)CC.CCOC(C)=O>CN1C(=O)CCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]([O:13][CH3:14])=[N:7][C:8]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:9][C:10]=1[CH3:11])=[O:4]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 57441127Methyl 6-chloro-2-methoxy-4-methylnicotinate

Product 1

HCID 866643212-Methoxy-4-methyl-6-morpholino-pyridine-3-carboxylic acid methylesterYield 45%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 5.0 g (21.8 mmol) 6-chloro-2-methoxy-4-methylpyridine-3-carboxylic acid methylester, 2.0 g (24.0 mmol) morpholine and 6.0 ml (43.5 mmol) NEt3 in NMP (21 ml) was heated at 90° C. for 2 d. After cooling to RT the mixture was partiotionated between EtOAc and a 1M aq. NaHCO3 sol. The organic layer was separated, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 4:1) provided 2.7 g (9.8 mmol, 45%) 2-methoxy-4-methyl-6-morpholino-pyridine-3-carboxylic acid methylester.

Workup

  1. customa 1M aq. NaHCO3 sol. The organic layer was separated
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by CC (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-bdef43dc9143456dbdca893e1d84c827
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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