Pyridine → 2-Fluoro-4-formylphenyl morpholine-4-carboxylate

HRID 1877762Notes

Reaction equation

HRID 1877762 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].C(Cl)Cl.N1C=CC=CC=1.[N:20]1([C:26](Cl)=[O:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>O>[N:20]1([C:26]([O:10][C:9]2[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=2[F:1])=[O:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 848104-Morpholinecarbonyl chlorideHCID 5872503-Fluoro-4-hydroxybenzaldehyde

Product 1

HCID 582346872-Fluoro-4-formylphenyl morpholine-4-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 250 mL dry round bottom flask were added 3-fluoro-4-hydroxybenzaldehyde (4.76 g, 34.0 mmol), anhydrous CH2Cl2 (40 mL) and pyridine (3.6 mL, 44.2 mmol). The mixture was stirred in an ice-water bath, then 4-morpholinecarbonyl chloride (4.4 mL, 37.4 mmol) was added. The mixture was stirred and warmed slowly to room temperature, then at room temperature overnight. Water (80 mL) was added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (50 mL×3). The combined CH2Cl2 solution was dried over Na2SO4. After removal of the solvent, the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give 2-fluoro-4-formylphenyl morpholine-4-carboxylate (7.45 g) as white solid. Yield: 87%. 1H NMR (CDCl3, 300 MHz): δ=9.97 (s, 1H), 7.74-7.70 (m, 2H), 7.45 (t, J=7.8 Hz, 1H), 3.81-3.61 (m, 8H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=189.9, 156.5, 153.1, 151.8, 144.0, 143.8, 135.0, 134.9, 126.7, 126.6, 124.8, 116.7, 116.4, 66.4, 66.3, 45.2, 44.4.

Workup

  1. customTo a 250 mL dry round bottom flask
  2. stirringThe mixture was stirred
  3. customat room temperature
  4. customovernight
  5. customThe CH2Cl2 layer was separated
  6. extractionthe aqueous layer was extracted continually with CH2Cl2 (50 mL×3)
  7. dry with materialThe combined CH2Cl2 solution was dried over Na2SO4
  8. customAfter removal of the solvent
  9. customthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Sources & evidence

ORD record
ord-b76334a44e1543189d5c8d711e72683b
Source dataset
uspto-grants-2012_11
Patent number
US08314081B2

Reaction notes

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