Allyl bromide → 2-Allyl-3-(3-fluoro-phenyl)-pentanedioic acid 1-methyl ester

HRID 2289164Notes

Reaction equation

HRID 2289164 reaction equation
[Li+].CC([N-][CH:6]([CH3:8])[CH3:7])C.[CH3:9][O:10][C:11](=[O:25])[CH2:12][CH:13]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1)[CH2:14][C:15]([OH:17])=[O:16].C(Br)C=C.CCN=C=NCCCN(C)C>C1COCC1.CN(C1C=CN=CC=1)C>[CH3:9][O:10][C:11](=[O:25])[CH:12]([CH2:8][CH:6]=[CH2:7])[CH:13]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1)[CH2:14][C:15]([OH:17])=[O:16]

Participants

7

Reactant 4

HCID 7841Allyl bromideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2724682Lithium diisopropylamideHCID 453589003-(3-Fluorophenyl)-5-methoxy-5-oxopentanoic acid

Product 1

HCID 544686422-Allyl-3-(3-fluoro-phenyl)-pentanedioic acid 1-methyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (-78° C.) solution of LDA (7.1 mL, 2.0 M, 14.2 mmol) in 50 mL THF was added a solution of 3-(3-fluoro-phenyl)-pentanedioic acid monomethyl ester (2-4) (1.58 g, 6.58 mmol) in 10 mL THF gradually. The mixture was stirred for 40 min, treated with allyl bromide (1.71 mL, 19.7 mmol) at -78° C. and stirred overnight while it was warmed to room temperature. It was then concentrated and diluted with 20 mL CH2Cl2 and 15 mL EtOH. To the resulting solution was added EDAC (1.88 g, 9.87 mmol) and DMAP (25 mg, 0.02 mmol). After stirring for 5 hr, the reaction was quenched with 20 mL 10% NaHCO3 and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to provide 2-5 as an oil, which was further purified using flash silica chromatography (Hexane/EtOAc, 4:1).

Workup

  1. stirringstirred overnight while it
  2. concentrationIt was then concentrated
  3. additiondiluted with 20 mL CH2Cl2 and 15 mL EtOH
  4. stirringAfter stirring for 5 hr
  5. customthe reaction was quenched with 20 mL 10% NaHCO3
  6. extractionextracted with EtOAc (×3)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-890de63308e34afea63bde5429652563
Source dataset
uspto-grants-2000_07
Patent number
US06090944

Reaction notes

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