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

HRID 1993016Notes

Reaction equation

HRID 1993016 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 3 L 3-neck flask equipped with a mechanical stirrer, nitrogen inlet, nitrogen outlet and 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 RB flask, compound 1.1 (35 g, 142 mmol) was dissolved in anhydrous THF (350 mL) with gentle warming. The solution of 1.1 was then 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 then quenched with aqueous NH4Cl (0.6N, 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 ethyl acetate (2×400 mL). The combined extracts were washed with saturated brine, dried over MgSO4, filtered, and concentrated to a light yellow solid (37 g, 91%). 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. customAn oven-dried 3 L 3-neck flask equipped with a mechanical stirrer, nitrogen inlet, nitrogen outlet
  2. customplaced in a room-temperature water bath
  3. customAfter purging with nitrogen for 20 minutes
  4. additiona solution of 1-propynylmagnesium bromide in THF (0.5 N, 600 mL) was added by cannula
  5. customIn a separate oven-dried
  6. customnitrogen-flushed 500 mL RB flask
  7. additionThe solution of 1.1 was then added over 15 minutes
  8. additionOver the course of the addition
  9. additionAfter the addition
  10. customquenched with aqueous NH4Cl (0.6N, 750 mL)
  11. additiondiluted with hexanes (800 mL)
  12. customThe layers were separated
  13. extractionextracted with ethyl acetate (2×400 mL)
  14. washThe combined extracts were washed with saturated brine
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated to a light yellow solid (37 g, 91%)

Sources & evidence

ORD record
ord-a0aa3f9a8ef54c95b12a08d72a89adbc
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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