Morpholine → HCID 66998215, compound

HRID 561009Notes

Reaction equation

HRID 561009 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>C1COCC1.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][N:5]=[CH:6][C:7]=1[C:8]([N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:10]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 682631,1'-CarbonyldiimidazoleHCID 8182294-Chloronicotinic acid

Product 1

HCID 66998215HCID 66998215, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Combine 4-chloronicotinic acid (0.10 g, 6.0 mmol) and 1,1′-carbonyldiimidazole (0.97 g, 6.0 mmol) in dry THF (15 mL). Stir at room temperature under nitrogen for 90 min. Add morpholine (1.58 mL, 18.0 mmol) and stir at room temperature under nitrogen for 15 hours. Dilute with dichloromethane, wash with saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride. Separate the layers and dry the organic layer over magnesium sulfate. Concentrate in vacuo. Purify the crude residue by column chromatography [5% to 25% (10% 2 M ammonia/methanol solution in dichloromethane)/dichloromethane] to give the title compound (1.17 g, 86%). MS (ES) m/z 227 [M+1]+.

Workup

  1. washwash with saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride
  2. customSeparate the layers
  3. dry with materialdry the organic layer over magnesium sulfate
  4. concentrationConcentrate in vacuo
  5. customPurify the crude residue by column chromatography [5% to 25% (10% 2 M ammonia/methanol solution in dichloromethane)/dichloromethane]

Sources & evidence

ORD record
ord-921c142360bf47a083375404a1cd4d7e
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Reaction notes

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