Acetaldehyde → HCID 86706087, compound

HRID 2176249Notes

Reaction equation

HRID 2176249 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)=[O:16].[CH:23](=[O:25])[CH3:24]>O1CCCC1>[CH3:13][O:14][C:15]([C:17]1([CH:23]([OH:25])[CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)=[O:16]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 7912DiisopropylamineHCID 13581853Methyl oxane-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 86706087HCID 86706087, compoundYield 113.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of N,N-diisopropylamine (909 mg, 1.25 mL, 9 mmol) in tetrahydrofuran (4 mL) was stirred at −78° C. under nitrogen. n-Butyllithium (3.6 mL, 9 mmol, 2.5 M solution in hexane) was added dropwise and the reaction mixture was stirred at −78° C. for 30 minutes. A solution of tetrahydro-pyran-2-carboxylic acid methyl ester (864 mg, 6 mmol) in tetrahydrofuran (8 mL) was added and the reaction mixture was stirred at −78° C. for 20 minutes. Acetaldehyde (792 mg, 1.0 mL, 18 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 pentane/diethyl ether 1:1 to 0:1 to afford the title compound (1.28 g) as an oil and as a 2:1 mixture of diastereoisomers. LCMS (m/z) 189.3 [M+H], Tr=1.23 min.

Workup

  1. stirringthe reaction mixture was stirred at −78° C. for 20 minutes
  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

Sources & evidence

ORD record
ord-42b508da4dcb4c8d984d6ea645bdecc7
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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