Benzaldehyde dimethyl acetal → HCID 89569177, compound

HRID 578745Notes

Reaction equation

HRID 578745 reaction equation
[OH:1][CH2:2][C@@:3]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:5][C@H:4]1[CH2:6][OH:7].CO[CH:15](OC)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1CCCCC1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>[C:16]1([CH:15]2[O:7][CH2:6][C@H:4]3[C@:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])([CH2:5]3)[CH2:2][O:1]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 2

HCID 62375Benzaldehyde dimethyl acetalHCID 10725903(1R,2R)-ethyl 1,2-bis(hydroxymethyl)cyclopropanecarboxylate

Product 1

HCID 89569177HCID 89569177, compoundYield 64.8%

Reagents, catalysts & solvents 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 8078CyclohexaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A solution of ethyl (1R,2R)-1,2-bis(hydroxymethyl)cyclopropanecarboxylate (10.5 kg, 60.3 mol) in cyclohexane (105.0 L) was added in a reactor. Then, benzaldehyde dimethylacetal (11.6 kg, 76.4 mol) followed by camphor sulfonic acid (73.0 g) was added into the reactor. The reaction mass was heated to reflux and a portion of solvent was distilled azeotropically. The progress of the reaction was monitored by HPLC. On completion of the reaction, the reaction mass was distilled to remove most of the solvent under reduced pressure below 45° C. To the concentrate, petroleum ether (32.0 L) was added and stirred to precipitate the product. The slurry was cooled to 0-5° C. and stirred for 15 min. The slurry was filtered and washed with cold petroleum ether (11.0 L). The product was dissolved in dichloromethane (210.0 L) and washed with water (52.0 L) followed by brine (53.0 L). The organic layer was dried over sodium sulfate (5.5 kg) and was distilled to remove most of the solvent. Petroleum ether (21.0 L) was added and stirred at 25-30° C. for 30 min to get the complete precipitation of the product. The slurry was further cooled to 0-5° C. and stirred for 60 min. The slurry was filtered and washed with cold petroleum ether (11.0 L). The product was dried in a vacuum tray dryer for 12 hours below 45-50° C. to afford 10.25 Kg (64.5%) of the title compound (4c).

Workup

  1. additionwas added into the reactor
  2. temperatureThe reaction mass was heated
  3. temperatureto reflux
  4. distillationa portion of solvent was distilled azeotropically
  5. customOn completion of the reaction
  6. distillationthe reaction mass was distilled
  7. customto remove most of the solvent under reduced pressure below 45° C
  8. additionTo the concentrate, petroleum ether (32.0 L) was added
  9. customto precipitate the product
  10. stirringstirred for 15 min
  11. filtrationThe slurry was filtered
  12. washwashed with cold petroleum ether (11.0 L)
  13. dissolutionThe product was dissolved in dichloromethane (210.0 L)
  14. washwashed with water (52.0 L)
  15. dry with materialThe organic layer was dried over sodium sulfate (5.5 kg)
  16. distillationwas distilled
  17. customto remove most of the solvent
  18. additionPetroleum ether (21.0 L) was added
  19. stirringstirred at 25-30° C. for 30 min
  20. customto get
  21. customthe complete precipitation of the product
  22. temperatureThe slurry was further cooled to 0-5° C.
  23. stirringstirred for 60 min
  24. filtrationThe slurry was filtered
  25. washwashed with cold petroleum ether (11.0 L)
  26. customThe product was dried in a vacuum tray dryer for 12 hours below 45-50° C.

Sources & evidence

ORD record
ord-954ebe87a94e4c6b9a162699071317c9
Source dataset
uspto-grants-2015_05
Patent number
US09040699B2

Reaction notes

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