Ethyl 3-oxocyclobutanecarboxylate → Ethyl 3-hydroxy-3-(4-methoxyphenyl)cyclobutanecarboxylate

HRID 920768Notes

Reaction equation

HRID 920768 reaction equation
[O:1]=[C:2]1[CH2:5][CH:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3]1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1>CCOCC>[OH:1][C:2]1([C:16]2[CH:17]=[CH:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)[CH2:5][CH:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3]1

Participants

4

Reactant 2

HCID 22467070Ethyl 3-oxocyclobutanecarboxylateHCID 178491912HCID 178491912, compound

Product 1

HCID 118062319Ethyl 3-hydroxy-3-(4-methoxyphenyl)cyclobutanecarboxylateYield 57%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of ethyl 3-oxocyclobutanecarboxylate (3.0 g, 21.1 mmol) in anhydrous Et2O (60 mL), cooled to −80° C., was added dropwise a solution of (4-methoxyphenyl)magnesium bromide (50.6 mL, 25.3 mmol, 2M in THF). The reaction mixture was allowed to warm to RT and stir for 2 h. The reaction mixture was quenched with a saturated aq. solution of NH4Cl (20 mL) and then extracted with EtOAc (3×30 mL) The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 279A as a colorless liquid (3 g, 57%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.42 (d, J=8.7 Hz, 2H), 6.89 (d, J=8.7 Hz, 2H), 5.58 (s, 1H), 4.08 (d, J=7.2 Hz, 2H), 3.75 (s, 3H), 2.76-2.67 (m, 1H), 2.60 (s, 2H), 2.47 (s, 2H), 1.22-1.16 (m, 3H).

Workup

  1. customThe reaction mixture was quenched with a saturated aq. solution of NH4Cl (20 mL)
  2. extractionextracted with EtOAc (3×30 mL) The combined organic layers
  3. washwere washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (40 g REDISEP® column, eluting with 15% EtOAc in hexanes)
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-4027f5041384418c99ad05b5b955c632
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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