Acetaldehyde → Tert-butyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclopentanecarboxylate

HRID 643540Notes

Reaction equation

HRID 643540 reaction equation
[Li+].CC([N-]C(C)C)C.[CH3:9][O:10][C:11]1([O:23][CH3:24])[CH2:15][CH2:14][CH:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]1.[CH:25](=[O:27])[CH3:26].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[OH:27][CH:25]([C:13]1([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:14][CH2:15][C:11]([O:23][CH3:24])([O:10][CH3:9])[CH2:12]1)[CH3:26]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 311Citric AcidHCID 2724682Lithium diisopropylamideHCID 58784445Tert-butyl 3,3-dimethoxycyclopentanecarboxylate

Product 1

HCID 57880496Tert-butyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclopentanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of LDA (2M in THF/heptane, 39 mL, 78 mmol) in THF (40 mL) was added dropwise over 15 min tert-butyl 3,3-dimethoxycyclopentanecarboxylate (15.0 g, 65.0 mmol) in 100 mL of THF. The resulting mixture was stirred at −78° C. for 40 min, then was treated dropwise with acetaldehyde (7.27 mL, 130 mmol). After stirring for an additional 45 min, the reaction mixture was poured into 500 mL of 10% citric acid solution. The mixture was extracted twice with ether and the combined ethereal layers were washed with brine. The ethereal layer was then dried over anhydrous MgSO4, filtered, and concentrated. TLC analysis indicated that the reaction had not gone to completion and a considerable amount of starting material was still present. Purification/separation by flash chromatography (silica, 30% ethyl acetateihexane) gave the tert-butyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclopentanecarboxylate as an approximately 1:1 ratio of threo and erythro diastereomer pairs and recovered tert-butyl 3,3-dimethoxycyclopentanecarboxylate.

Workup

  1. stirringAfter stirring for an additional 45 min
  2. extractionThe mixture was extracted twice with ether
  3. washthe combined ethereal layers were washed with brine
  4. dry with materialThe ethereal layer was then dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification/separation by flash chromatography (silica, 30% ethyl acetateihexane)

Sources & evidence

ORD record
ord-3fa2a303db0045ab8ca2f0760a8d3216
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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