Benzyl Alcohol → Dibenzyl 2-fluoromalonate

HRID 2373067Notes

Reaction equation

HRID 2373067 reaction equation
[F:1][CH:2]([C:7]([O:9][CH3:10])=[O:8])[C:3]([O:5][CH3:6])=[O:4].C(O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O.[C:20]1(C)[CH:25]=[CH:24][C:23](S(O)(=O)=O)=[CH:22][CH:21]=1>C1(C)C=CC=CC=1>[F:1][CH:2]([C:7]([O:9][CH2:10][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:8])[C:3]([O:5][CH2:6][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:4]

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 521998p-Toluenesulfonic acid monohydrateHCID 2737111Dimethyl fluoromalonate

Product 1

HCID 23254375Dibenzyl 2-fluoromalonateYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A 3-neck, 5-L round-bottom flask equipped with a vacuum distillation head, a thermometer, and a magnetic stir bar was charged with dimethyl fluoromalonate (339 g assayed at 83% purity by VPC, 1.88 mol), benzyl alcohol (935 mL, 9.04 mol), toluene (846 mL), and p-toluenesulfonic acid monohydrate (21.5 g, 0.113 mol). The mixture was heated under vacuum (10-15 inches of Hg) until all of the toluene had distilled, then at 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C. The progress of the reaction was monitored by 19F NMR. After a total of 7 hours, the heat was removed, and the mixture was allowed to cool, with continued stirring. When the temperature had lowered to 75° C., isopropanol (450 mL) was added. When the temperature had lowered to 55° C., hexane (1 L) was added. The product crystallized out and the mixture was placed in the freezer overnight. The product was filtered, washed with hexane (2×1 L), sucked dry, and dried overnight in vacuo. The yield was 452 g (96% pure by weight). A second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%.

Workup

  1. distillationhad distilled
  2. temperatureat 28-29 inches of Hg (water aspirator vacuum), the reaction temperature being maintained at 100° to 115° C
  3. customAfter a total of 7 hours, the heat was removed
  4. temperatureto cool, with continued stirring
  5. customhad lowered to 75° C.
  6. additionisopropanol (450 mL) was added
  7. customhad lowered to 55° C.
  8. additionhexane (1 L) was added
  9. customThe product crystallized out
  10. customwas placed in the freezer overnight
  11. filtrationThe product was filtered
  12. washwashed with hexane (2×1 L)
  13. customsucked dry
  14. customdried overnight in vacuo
  15. customA second crop of 29 g was obtained from the combined filtrates and washings, for a total yield of 81%

Sources & evidence

ORD record
ord-143d7b3ccac947f1bc58c6520ef9d734
Source dataset
uspto-grants-1992_03
Patent number
US05101068

Reaction notes

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