Benzyl Alcohol → Dibenzyl 2-fluoromalonate

HRID 248586Notes

Reaction equation

HRID 248586 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 (2xl 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 (2xl 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-b2c389627e4b431caeeda82654acf7b8
Source dataset
uspto-grants-1993_05
Patent number
US05210272

Reaction notes

Loading…