Tetrahydrofuran → 5-(1-(4-Hydroxyphenyl)but-2-yn-1-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione

HRID 2375723Notes

Reaction equation

HRID 2375723 reaction equation
[OH:1][C:2]1[CH:18]=[CH:17][C:5]([CH:6]=[C:7]2[C:12](=[O:13])[O:11][C:10]([CH3:15])([CH3:14])[O:9][C:8]2=[O:16])=[CH:4][CH:3]=1.[CH2:19]1[CH2:23]OC[CH2:20]1>>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]([CH:7]2[C:8](=[O:16])[O:9][C:10]([CH3:15])([CH3:14])[O:11][C:12]2=[O:13])[C:20]#[C:19][CH3:23])=[CH:17][CH:18]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 3705415-(4-Hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 598551335-(1-(4-Hydroxyphenyl)but-2-yn-1-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione

Procedure

An oven-dried 3L 3-neck flask equipped with a mechanical stirrer, nitrogen inlet and nitrogen outlet was placed in a room-temperature water bath. After purging with nitrogen for 20 minutes, a solution of 1-propynylmagnesium bromide in THF (0.5 N, 600 mL) was added by cannula. In a separate oven-dried and nitrogen-flushed 500 mL round bottom flask, compound 1.1 (35 g, 142 mmol) was dissolved in anhydrous THF (350 mL) with gentle warming. The solution of 1.1 was added over 15 minutes. Over the course of the addition, the reaction mixture changed to a thick, yellow suspension. After the addition was complete, the reaction mixture was stirred for 15 minutes and quenched with aqueous NH4Cl (0.6 N, 750 mL) and diluted with hexanes (800 mL). The layers were separated and the organic layer discarded. The aqueous layer was acidified to pH ˜2 with saturated aqueous KHSO4 and extracted with EtOAc (2×400 mL). The combined extracts were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a light yellow solid (37 g). 1H NMR (500 MHz, acetone-d6) δ 8.26 (s, 1H); 7.39 (d, 2H, J=8.5 Hz); 6.76 (d, 2H, J=8.4 Hz); 4.73 (br s, 1H); 4.46 (d, 1H, J=2.4 Hz); 1.82 (s, 3H); 1.81 (s, 3H); 1.64 (s, 3H). MS ESI (pos.) m/e: 599.0 (2M+Na).

Workup

  1. dry with materialAn oven-dried 3L 3-neck flask
  2. customequipped with a mechanical stirrer, nitrogen inlet and nitrogen outlet
  3. customwas placed in a room-temperature water bath
  4. customAfter purging with nitrogen for 20 minutes
  5. additiona solution of 1-propynylmagnesium bromide in THF (0.5 N, 600 mL) was added by cannula
  6. customIn a separate oven-dried
  7. customnitrogen-flushed 500 mL round bottom flask
  8. additionThe solution of 1.1 was added over 15 minutes
  9. additionOver the course of the addition
  10. additionAfter the addition
  11. customquenched with aqueous NH4Cl (0.6 N, 750 mL)
  12. additiondiluted with hexanes (800 mL)
  13. customThe layers were separated
  14. extractionextracted with EtOAc (2×400 mL)
  15. washThe combined extracts were washed with saturated brine
  16. dry with materialdried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated to a light yellow solid (37 g)

Sources & evidence

ORD record
ord-4d910a4c7b014033ad8faa952aaa46cc
Source dataset
uspto-grants-2008_12
Patent number
US07465804B2

Reaction notes

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