Pyridine → 3,5-Difluoro-4-formylphenyl isopropyl carbonate

HRID 1877766Notes

Reaction equation

HRID 1877766 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([F:11])[C:3]=1[CH:4]=[O:5].C(Cl)Cl.N1C=CC=CC=1.Cl[C:22]([O:24][CH:25]([CH3:27])[CH3:26])=[O:23]>C1(C)C=CC=CC=1.O>[C:22](=[O:23])([O:24][CH:25]([CH3:27])[CH3:26])[O:10][C:8]1[CH:9]=[C:2]([F:1])[C:3]([CH:4]=[O:5])=[C:6]([F:11])[CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 7917Isopropyl chloroformateHCID 249035482,6-Difluoro-4-hydroxybenzaldehyde

Product 1

HCID 582347263,5-Difluoro-4-formylphenyl isopropyl carbonateYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a 250 mL dry round bottom flask were added 2,6-difluoro-4-hydroxy-benzaldehyde (4.80 g, 30.4 mmol), anhydrous CH2Cl2 (30 mL) and pyridine (3.0 mL, 36.5 mmol). The mixture was stirred in an ice-water bath, then a solution of isopropyl chloroformate in toluene (1.0 M, 33.4 mL) was added. After stirring at 0° C. for 2 hours, the mixture was stirred 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 (80 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 3,5-difluoro-4-formylphenyl isopropyl carbonate (6.20 g) as a colorless oil. Yield: 84%. 1H NMR (CDCl3, 300 MHz): δ=10.30 (s, 1H), 7.02-6.96 (m, 2H), 5.03 (seventet, J=6.3 Hz, 1H), 1.43 (d, J=6.3 Hz, 6H). 13C NMR (CDCl3, 75.5 MHz): δ=183.3, 163.6 (dd, J=262.5, 7.92 Hz), 156.3 (t, J=15.2 Hz), 151.1, 111.9 (t, J=11.5 Hz), 106.0 (dd, J=25.1, 3.62 Hz), 74.5, 21.5. 19F NMR (CDCl3, 282.3 MHz): δ=−113.0 (d, J=9.0 Hz).

Workup

  1. customTo a 250 mL dry round bottom flask
  2. stirringAfter stirring at 0° C. for 2 hours
  3. stirringthe mixture was stirred at room temperature overnight
  4. customThe CH2Cl2 layer was separated
  5. extractionthe aqueous layer was extracted continually with CH2Cl2 (80 mL×3)
  6. dry with materialThe combined CH2Cl2 solution was dried over Na2SO4
  7. customAfter removal of the solvent
  8. customthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Sources & evidence

ORD record
ord-e10588f6a5bb4288b88f79b275104879
Source dataset
uspto-grants-2012_11
Patent number
US08314081B2

Reaction notes

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