Methyl acetoacetate → 5-Cyclopentyl-5-hydroxy-9-(4-hydroxy-2,5-dimethyl-phenyl)-3-oxo-non-8-ynoic Acid Methyl Ester

HRID 858861Notes

Reaction equation

HRID 858861 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]([O:15][CH3:16])(=[O:14])[CH2:10][C:11]([CH3:13])=[O:12].[CH:17]1([C:22](=[O:36])[CH2:23][CH2:24][C:25]#[C:26][C:27]2[CH:32]=[C:31]([CH3:33])[C:30]([OH:34])=[CH:29][C:28]=2[CH3:35])[CH2:21][CH2:20][CH2:19][CH2:18]1>C1COCC1>[CH3:16][O:15][C:9](=[O:14])[CH2:10][C:11](=[O:12])[CH2:13][C:22]([CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)([OH:36])[CH2:23][CH2:24][C:25]#[C:26][C:27]1[CH:32]=[C:31]([CH3:33])[C:30]([OH:34])=[CH:29][C:28]=1[CH3:35]

Participants

5

Reactant 3

HCID 7757Methyl acetoacetateHCID 2724682Lithium diisopropylamideHCID 587625021-Cyclopentyl-5-(4-hydroxy-2,5-dimethyl-phenyl)-pent-4-yn-1-one

Product 1

HCID 587623975-Cyclopentyl-5-hydroxy-9-(4-hydroxy-2,5-dimethyl-phenyl)-3-oxo-non-8-ynoic Acid Methyl EsterYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a freshly prepared solution of LDA (1 M, 2.2 mL, 2.2 mmol) cooled to 0° C. was added methyl acetoacetate (0.12 mL, 1.1 mmol) dissolved in THF (1 mL). After stirring for 30 minutes, 1-cyclopentyl-5-(4-hydroxy-2,5-dimethyl-phenyl)-pent-4-yn-1-one (0.10 g, 0.37 mmol) from Step 1 above dissolved in THF (1 mL) was added. The reaction was stirred for 1 hour, and then warmed to room temperature. After quenching with 10 mL saturated ammonium chloride, the layers were separated. The aqueous layer was extracted with 2×15 mL CH2Cl2, and the organic layers were combined. After drying over Na2SO4, and filtering to remove the solids, the mother liquor was concentrated to an oil. Flash chromatography of the oil gave the desired product (69 mg, 48% yield).

Workup

  1. additionwas added
  2. stirringThe reaction was stirred for 1 hour
  3. customAfter quenching with 10 mL saturated ammonium chloride
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with 2×15 mL CH2Cl2
  6. dry with materialAfter drying over Na2SO4
  7. filtrationfiltering
  8. customto remove the solids
  9. concentrationthe mother liquor was concentrated to an oil

Sources & evidence

ORD record
ord-ec9771eb0d7143eb93ac6a42f99719c9
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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