Acetaldehyde → HCID 86706167, compound

HRID 2176319Notes

Reaction equation

HRID 2176319 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21]([CH:23]1[CH2:28][O:27][C:26]([CH3:30])([CH3:29])[CH2:25][O:24]1)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:31](=[O:33])[CH3:32]>O1CCCC1>[CH2:13]([O:20][C:21]([C:23]1([CH:31]([OH:33])[CH3:32])[CH2:28][O:27][C:26]([CH3:30])([CH3:29])[CH2:25][O:24]1)=[O:22])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 7912DiisopropylamineHCID 86706166HCID 86706166, compoundHCID 178418339Butyllithium

Product 1

HCID 86706167HCID 86706167, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of N,N-diisopropylamine (530 mg, 0.73 mL, 5.25 mmol) in anhydrous tetrahydrofuran (4 mL) was stirred at −78° C. under nitrogen. n-Butyl lithium (2.1 mL, 5.25 mmol, 2.5 M solution in hexane) was added dropwise and the reaction mixture was stirred at −78° C. for 30 min. A solution of 5,5-dimethyl-[1,4]dioxane-2-carboxylic acid benzyl ester (870 mg, 3.5 mmol) in tetrahydrofuran (8 mL) was added and the reaction mixture was stirred at −78° C. for 20 min. Acetaldehyde (462 mg, 0.6 mL, 10.5 mmol) was added in one portion. The cooling bath was removed and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to 0° C. and ice-cold hydrochloric acid (2 M) was added to acidify the reaction mixture to pH 2. Sodium chloride was added to saturate the aqueous phase and the mixture was extracted with diethyl ether. The organic extracts were combined and washed with brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 6:1 to 0:1 followed by silica gel chromatography using iso-hexanes/ethyl acetate 3:1 to 0:1 to the title compound (400 mg, 40%) as an oil and as a 2:1 mixture of diastereoisomers. LCMS (m/z) 295.1 [M+H], Tr=2.11 min.

Workup

  1. stirringthe reaction mixture was stirred at −78° C. for 20 min
  2. customThe cooling bath was removed
  3. stirringthe reaction mixture was stirred at room temperature for 1 h
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. additionice-cold hydrochloric acid (2 M) was added
  6. additionSodium chloride was added
  7. concentrationto saturate the aqueous phase
  8. extractionthe mixture was extracted with diethyl ether
  9. washwashed with brine
  10. filtrationThe organic solution was filtered through a hydrophobic frit
  11. customthe filtrate was evaporated
  12. customThe residue was purified by silica gel chromatography
  13. additionas a 2:1 mixture of diastereoisomers
  14. customLCMS (m/z) 295.1 [M+H], Tr=2.11 min.

Sources & evidence

ORD record
ord-94cc869c334a4dc4a11ecfa5bc899ae3
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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