Benzaldehyde → (2R,3R)-3-benzyloxy-2-butyloctanoic acid

HRID 1695172Notes

Reaction equation

HRID 1695172 reaction equation
C([O:5][C:6](=[O:19])[C@H:7]([CH2:15][CH2:16][CH2:17][CH3:18])[C@H:8]([OH:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])(C)(C)C.C(N(CC)CC)C.C[Si](C)(C)Cl.[CH:32](=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C([SiH](CC)CC)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.[Na].[H][H]>ClCCl>[CH2:32]([O:14][C@H:8]([CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C@@H:7]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]([OH:5])=[O:19])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

9

Reactant 7

HCID 240BenzaldehydeHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 65367Trimethylsilyl triflateHCID 86645802(2R,3R)-2-butyl-3-hydroxyoctanoic acid t-butyl esterHCID 178506446HCID 178506446, compound

Product 1

HCID 67274216(2R,3R)-3-benzyloxy-2-butyloctanoic acidYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The (2R,3R)-2-butyl-3-hydroxyoctanoic acid t-butyl ester (1.00 g, 3.67 mmol) obtained in Production Example C-1 was dissolved in anhydrous dichloromethane (12 ml). Triethylamine (1.37 g, 13.6 mmol) and trimethylchlorosilane (1.20 g, 11.0 mmol) were added to this solution, which was stirred for 30 minutes at room temperature. Then, distilled water was added thereto, and extracted 3 times with dichloromethane. The resulting organic layer was dried with anhydrous magnesium sulfate, filtered, and condensed. The crude product was dissolved in anhydrous dichloromethane (69 ml), and then cooled to −48° C. Benzaldehyde (584 mg, 5.51 mmol), triethylsilane (641 mg, 5.51 mmol), and trimethylsilyl triflate (408 mg, 1.84 mmol) were sequentially added thereto; the mixture was stirred at −48° C. for 15 minutes, and then warmed to room temperature. After the reaction of 2 hours, an aqueous saturated sodium hydrogen solution was added thereto to be washed. The resulting organic layer was dried with anhydrous magnesium sulfate, filtered, and condensed. The obtained residue was purified by column chromatography (silica gel: 30 g, n-hexane/ethyl acetate=7/1) to produce the target compound (781 mg, 70%).

Workup

  1. distillationThen, distilled water
  2. additionwas added
  3. extractionextracted 3 times with dichloromethane
  4. dry with materialThe resulting organic layer was dried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customcondensed
  7. temperaturecooled to −48° C
  8. stirringthe mixture was stirred at −48° C. for 15 minutes
  9. temperaturewarmed to room temperature
  10. customAfter the reaction of 2 hours
  11. washto be washed
  12. dry with materialThe resulting organic layer was dried with anhydrous magnesium sulfate
  13. filtrationfiltered
  14. customcondensed
  15. customThe obtained residue was purified by column chromatography (silica gel: 30 g, n-hexane/ethyl acetate=7/1)

Sources & evidence

ORD record
ord-b23014e40e4a49bfa9d3a347d926d2d1
Source dataset
uspto-grants-2012_04
Patent number
US08163713B2

Reaction notes

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