Hydrochloric Acid → HCID 69059851, compound

HRID 2103002Notes

Reaction equation

HRID 2103002 reaction equation
C([O:4][C:5]1[C:10]([CH3:11])=[C:9]([CH3:12])[C:8]([OH:13])=[C:7]([C:14](=[O:16])[CH3:15])[C:6]=1[CH3:17])(=O)C.[C:18]1(=O)[CH2:21][CH2:20][CH2:19]1.N1CCCC1.Cl>C1(C)C=CC=CC=1.[OH-].[Na+].CO.O>[OH:4][C:5]1[C:6]([CH3:17])=[C:7]2[C:8](=[C:9]([CH3:12])[C:10]=1[CH3:11])[O:13][C:18]1([CH2:21][CH2:20][CH2:19]1)[CH2:15][C:14]2=[O:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14496CyclobutanoneHCID 31268PyrrolidineHCID 9859505HCID 9859505, compound

Product 1

HCID 69059851HCID 69059851, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 14798Sodium HydroxideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of the above solid 3-acetyl-4-hydroxy-2,5,6-trimethylphenyl acetate (35 g) in 150 mL of toluene was added cyclobutanone (11.4 g) and pyrrolidine (15 mL). The reaction was allowed to reflux for 2 hours and water from the reaction was removed using a Dean-Stark apparatus. After the reaction was complete, the mixture was extracted with ethyl acetate and washed with 1N HCl and water. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to give 34 g of acetyl-protected product as a dark brown residue. This residue was hydrolyzed in 1N NaOH in MeOH/water for 3 hours. After the reaction was complete as indicated by TLC, the mixture was acidified with 1N HCl and extracted with ethyl acetate and dried over anhydrous Na2SO4. After concentration in vacuo, the resulting dark brown residue (30 g) was loaded onto a short silica gel column, and eluted with 10-40% ethyl acetate in hexane. Recrystallization of the resulting product from ethyl acetate and hexane gave 14.6 g of the desired 6-hydroxy-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one as a yellow solid. The mother liquid was concentrated to give another 4 g of crude 6-hydroxy-5,7,8-trimethylspiro[chromene-2,1′-cyclobutan]-4(3H)-one as a dark brown residue that can further be purified as described above. 1H-NMR (300 MHz, CDCl3) δ=4.61 (s, 1H), 2.86 (s, 2H), 2.56 (s, 3H), 2.30-1.70 (m, 12H) ppm. 13C-NMR (75 MHz, CDCl3) δ=195.3, 152.8, 146.2, 132.3, 124.2, 120.9, 117.3, 79.6, 47.7, 33.2, 13.4, 12.9, 12.4, 12.3 ppm. MS: m/z=247.1 (M+H+)

Workup

  1. temperatureto reflux for 2 hours
  2. customwater from the reaction was removed
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with 1N HCl and water
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto give 34 g of acetyl-
  8. extractionextracted with ethyl acetate
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationAfter concentration in vacuo
  11. washeluted with 10-40% ethyl acetate in hexane
  12. customRecrystallization of the resulting product from ethyl acetate and hexane

Sources & evidence

ORD record
ord-2d0d6afb5c204169b5ae611be8bbd8ef
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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