Tetrahydrofuran → Ethyl 2-cyclopropyl-2-(2-pyridyl)hydroxyacetate

HRID 1058286Notes

Reaction equation

HRID 1058286 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7](=[O:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:14]1[CH2:18]OC[CH2:15]1>C1([Mg]Br)CC1>[CH:15]1([C:7]([OH:13])([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:14][CH2:18]1

Participants

4

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 9989820Ethyl 2-pyridineglyoxylate

Product 1

HCID 18672421Ethyl 2-cyclopropyl-2-(2-pyridyl)hydroxyacetate

Reagents, catalysts & solvents 1

HCID 178418630HCID 178418630, compoundSolvent

Procedure

To a stirred solution of ethyl 2-(2-pyridyl)-2-oxoacetate (1.0 g, 5.6 mmol) in 10 mL of THF at −78° C. under nitrogen atmosphere was added in 0.92M cyclopropyl magnesium bromide in THF solution (6.7 mL, 7.3 mmol). The reaction was then allowed to equilibrate to 0° C. and stir for 1 h. The reaction was quenched with saturated NH4Cl solution and partitioned between EtOAc and water. The EtOAc layer was separated, dried over anhydrous Na2SO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue was purified by flash silica gel chromatography using 1% methanol in dichloromethane as an eluent. After concentration of desired fractions in vacuo ethyl 2-cyclopropyl-2-(2-pyridyl)hydroxyacetate was obtained as a yellow oil (0.9 g; 1H NMR, 400 MHz, CDCl3, 8.52 ppm (d, 1H), 7.76 ppm (m, 2H), 7.25 ppm (m, 1H), 5.18 ppm (s, 1H), 4.23 ppm (q, 2H), 1.8 ppm (m, 1H), 1.24 ppm (t, 3H), 0.72 ppm (m, 1H), 0.47 ppm (m, 2H), 0.37 ppm (m, 1H)).

Workup

  1. customto equilibrate to 0° C.
  2. customThe reaction was quenched with saturated NH4Cl solution
  3. custompartitioned between EtOAc and water
  4. customThe EtOAc layer was separated
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customThe filtrate solvent was removed under reduced pressure
  8. customthe residue was purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-20139b2c02394e28bf9b4931ba40e555
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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