Diisopropylamine → 6-[2-cyclopentyl-4-(3-fluoro-4-isopropylphenyl)-2-hydroxybut-3-ynyl]-2,2-dimethyl-4H-1,3-dioxin-4-one

HRID 858589

Reaction equation

HRID 858589 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[C:4]([F:11])[CH:3]=1.[CH:12]1([C:17]([OH:30])([C:28]#[CH:29])[CH2:18][C:19]2[O:24][C:23]([CH3:26])([CH3:25])[O:22][C:21](=[O:27])[CH:20]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.C(NC(C)C)(C)C>CN(C=O)C.CCOC(C)=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:12]1([C:17]([OH:30])([C:28]#[C:29][C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[C:4]([F:11])[CH:3]=2)[CH2:18][C:19]2[O:24][C:23]([CH3:26])([CH3:25])[O:22][C:21](=[O:27])[CH:20]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

8

Reactant 3

HCID 7912DiisopropylamineHCID 210510924-Bromo-2-fluoro-1-(1-methylethyl)benzeneHCID 224998026-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one

Product 1

HCID 587625876-[2-cyclopentyl-4-(3-fluoro-4-isopropylphenyl)-2-hydroxybut-3-ynyl]-2,2-dimethyl-4H-1,3-dioxin-4-oneYield 89.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-2-fluoro-1-isopropylbenzene (5.0 g, 23.2 mmol), 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (5.56 g, 21.0 mmol) were dissolved in anhydrous DMF (30 mL). To this solution, CuI (120 mg, 0.63 mmol), Pd(PPh3)2Cl2 (0.59 g, 0.84 mmol), and diisopropylamine (60 mL), were added sequentially. The mixture was then heated at 90° C. for 20 min before it was cooled down to 25° C. The reaction was diluted with EtOAc (150 mL) and washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (040% EtOAc in hexanes) to give the desired product (7.5 g, 81% yield).

Workup

  1. temperaturewas cooled down to 25° C
  2. washwashed with aqueous NH4Cl, brine
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by flash column chromatography (040% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2caacc4625404161ba0665d00f684cee
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Linked notes

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