4-Methylmorpholine → HCID 58523840, compound

HRID 1446713Notes

Reaction equation

HRID 1446713 reaction equation
Cl.[C:2]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].C[N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C1COCC1.N1CCOCC1>ClCCl>[C:2]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:14])[CH:7]=1)([CH3:3])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 8028TetrahydrofuranHCID 8083MorpholineHCID 144823814-(tert-Butyl)picolinic acid hydrochloride

Product 1

HCID 58523840HCID 58523840, compoundYield 79.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Suspend 4-tert-butyl-pyridine-2-carboxylic acid hydrochloride (11.14 g, 51.8 mmol) in 50 mL dichloromethane, add 4-methylmorpholine (10.48 g, 11.4 mL, 104 mmol), stir, add 100 mL THF and stir the suspension a few minutes. Add N,N′-carbonyldiimidazole (8.4 g, 51.8 mmol) to the stirring suspension, note moderate gas evolution and stir the light suspension at room temperature for 30 to 90 minutes. Add morpholine (13.54 g, 13.61 mL, 155 mmol) via pipet, stir overnight at room temperature. Dilute the suspension with 400 mL dichloromethane, wash with 400 mL saturated aqueous sodium bicarbonate solution and back-extract the aqueous phase with 100 mL dichloromethane. Combine organic layers and wash with 300 mL portions of saturated sodium bicarbonate (once) and dilute aqueous saturated sodium chloride (three times). Dry the organic layers over MgSO4 concentrate to an oil and purify on a 400 g silica cartridge with a gradient of 0→10% acetone in EtOAc over 20 minutes. Pool, concentrate, and dry fractions to provide 10.24 grams of a viscous colorless oil. LCMS (ES) m/z 249 (M+1).

Workup

  1. stirringstir the suspension a few minutes
  2. stirringstir the light suspension at room temperature for 30 to 90 minutes
  3. washwash with 400 mL saturated aqueous sodium bicarbonate solution
  4. extractionback-extract the aqueous phase with 100 mL dichloromethane
  5. washCombine organic layers and wash with 300 mL portions of saturated sodium bicarbonate (once) and dilute aqueous saturated sodium chloride (three times)
  6. dry with materialDry the organic layers over MgSO4
  7. concentrationconcentrate to an oil
  8. custompurify on a 400 g silica cartridge with a gradient of 0→10% acetone in EtOAc over 20 minutes
  9. concentrationPool, concentrate
  10. customdry fractions

Sources & evidence

ORD record
ord-4d62d687e11f433192b5ea15b07f6772
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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