4-Bromoanisole → HCID 22499792, compound

HRID 1815116Notes

Reaction equation

HRID 1815116 reaction equation
[CH:1]1([C:6]([OH:19])([C:17]#[CH:18])[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1.C(NC(C)C)(C)C>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.O1CCOCC1>[CH:1]1([C:6]([OH:19])([C:17]#[C:18][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 3

HCID 77304-BromoanisoleHCID 7912DiisopropylamineHCID 224998026-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one

Product 1

HCID 22499792HCID 22499792, compoundYield 67%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-(2-cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one (66 mg, 0.25 mmol), 4-bromoanisole (34.4 μL, 0.275 mmol), diisopropylamine(42.4 μL, 0.30 mmol), P(t-Bu)3 (30 μL of 10% by weight solution in hexanes, 0.015 mmol), and anhydrous dioxane (220 μL), under argon, was added Pd(PhCN)2Cl2 (2.87 mg, 0.0075 mmol), and CuI (0.95 mg, 0.005 mmol), at room temperature. The reaction was vacuum-flushed with argon (3×), then stirred at room temperature for 2.5 hours. HPLC at this time indicated −60% conversion. The reaction was then placed in a 35° C. oil bath for an additional 2 hours, at which time all starting material had been consumed. The reaction was concentrated and purified by silica gel chromatography-eluted with 30% ethytacetate/hexanes, which gave 62 mg of the product (67% yield). 1H NMR (CDCl3): δ 1.63 (m, 4H), 1.72 (s, 3H), 1.73 (s, 3H), 2.23 (pentet, 1H, J=8.0 Hz), 2.54(s, 1H), 2.65 (s, 2H), 3.81 (s, 3H), 5.47 (s, 1H), 6.83 (d, 2H, J=8.7 Hz), 7.31 (d, 2H, J=8.1 Hz); ESIMS (M+Na+): 393.2.

Workup

  1. customat room temperature
  2. customThe reaction was vacuum-flushed with argon (3×)
  3. customwas then placed in a 35° C.
  4. customfor an additional 2 hours
  5. customat which time all starting material had been consumed
  6. concentrationThe reaction was concentrated
  7. custompurified by silica gel
  8. washchromatography-eluted with 30% ethytacetate/hexanes, which

Sources & evidence

ORD record
ord-f0876e5816334dd7adc1aaabaa34e370
Source dataset
uspto-grants-2005_04
Patent number
US06878727B2

Reaction notes

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