6-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one → {4-[3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)but-1-ynyl]-2-ethylphenoxy}acetonitrile

HRID 858645

Reaction equation

HRID 858645 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][C:8]#[N:9])=[C:4]([CH2:12][CH3:13])[CH:3]=1.[CH:14]1([C:19](O)([C:30]#[CH:31])[CH2:20][C:21]2[O:26][C:25]([CH3:28])([CH3:27])[O:24][C:23](=[O:29])[CH:22]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1>C(NC(C)C)(C)C.CN(C=O)C.[NH4+].[Cl-].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.[Cu]I>[CH:14]1([CH:19]([CH2:20][C:21]2[O:26][C:25]([CH3:27])([CH3:28])[O:24][C:23](=[O:29])[CH:22]=2)[C:30]#[C:31][C:2]2[CH:11]=[CH:10][C:5]([O:6][CH2:7][C:8]#[N:9])=[C:4]([CH2:12][CH3:13])[CH:3]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

8

Reactant 2

HCID 224998026-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-oneHCID 22688480(4-Bromo-2-ethylphenoxy)acetonitrile

Product 1

HCID 68868806{4-[3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)but-1-ynyl]-2-ethylphenoxy}acetonitrileYield 61.6%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 7912DiisopropylamineSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution (4-bromo-2-ethylphenoxy)acetonitrile (1.99 g, 8.33 mmol) in diisopropylamine (9 mL) and DMF (3 mL) was added 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (2.00 g, 7.57 mmol), PdCl2(PPh3)2 (211 mg, 4 mol %), CuI (115 mg, 8 mol %). The mixture was heated to 90° C. for 30 min before it was cooled down to room temperature. The reaction was diluted with aqueous NH4Cl, extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (10–50% EtOAc in hexanes) to give the product (1.9 g). 1H NMR (300 MHz, CDCl3) δ: 1.23 (t, J=12.07 Hz, 3H) 1.35–1.80 (m, 14H), 2.30 (m, 1H), 3.50 (m, 5 H), 4.62 (s, 2 H), 4.87 (s, 1 H), 6.90 (d, J=2.54 Hz, 1 H), 7.14 (m, 1 H), 7.38 (m, 1 H).

Workup

  1. temperaturewas cooled down to room temperature
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried with Na2SO4
  5. customevaporated to dryness
  6. customThe mixture was purified by flash column chromatography (10–50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0527e7f585d84149b46813d01fac02b1
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Linked notes

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