Isobutyraldehyde → HCID 59356020, compound

HRID 660970Notes

Reaction equation

HRID 660970 reaction equation
N(C(C)C)C(C)C.[Li]CCCC.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[CH:23](=[O:27])[CH:24]([CH3:26])[CH3:25]>C1COCC1>[CH2:21]([O:20][C:18]([C:14]1[S:13][C:17]([CH:23]([OH:27])[CH:24]([CH3:26])[CH3:25])=[CH:16][CH:15]=1)=[O:19])[CH3:22]

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 7912DiisopropylamineHCID 76052Ethyl 2-thenoateHCID 178418339Butyllithium

Product 1

HCID 59356020HCID 59356020, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of i-Pr2NH (1.26 mL, 9.20 mmol) in THF (35 mL) at −78° C. is treated with n-BuLi (5.6 mL, 1.6M, 9.0 mmol) over the course of 3 minutes. The solution is warmed to rt for 10 min., then recooled to 78° C. Ethyl 2-thiophene carboxylate (1.00 mL, 7.44 mmol) is added dropwise and the resulting solution is stirred for 15 min., then isobutyraldehyde (0.81 mL, 9.14 mmol) is added and the reaction is warmed to rt and stirred overnight. The resulting solution is quenched with saturated NH4Cl (25 mL) and extracted with EtOAc (2×50 mL). Combined extracts are washed with H2O, brine, dried over MgSO4, filtered, and concentrated. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 0% to 30% EtOAc giving 5-(1-hydroxy-2-methyl-propyl)-thiophene-2-carboxylic acid ethyl ester (1.25 g, 73%) as a yellow oil. MS (ES): 211.1 [M+H−H2O]+.

Workup

  1. customrecooled to 78° C
  2. temperaturethe reaction is warmed to rt
  3. stirringstirred overnight
  4. customThe resulting solution is quenched with saturated NH4Cl (25 mL)
  5. extractionextracted with EtOAc (2×50 mL)
  6. washCombined extracts are washed with H2O, brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluted with hexanes using a gradient of 0% to 30% EtOAc

Sources & evidence

ORD record
ord-ecf034740c4042f68b163f6bdf27e7af
Source dataset
uspto-grants-2011_12
Patent number
US08084489B2

Reaction notes

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