Methanol → [6-Ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro isobenzofuran-5-yl]-acetaldehyde

HRID 540715

Reaction equation

HRID 540715 reaction equation
[CH2:1]([C:4]1[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[C:11]2[C:7]([CH2:8][O:9][C:10]2=[O:20])=[C:6]([CH3:21])[C:5]=1[CH2:22][CH3:23])[CH:2]=C.NC(N)=S.C[OH:29]>C(Cl)Cl.N1C=CC=CC=1>[CH2:22]([C:5]1[C:6]([CH3:21])=[C:7]2[C:11]([C:10](=[O:20])[O:9][CH2:8]2)=[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:18])([CH3:19])[CH3:17])[C:4]=1[CH2:1][CH:2]=[O:29])[CH3:23]

Participants

6

Reactant 3

HCID 887MethanolHCID 2723790ThioureaHCID 574598636-Allyl-5-ethyl-4-methyl-7-(2-trimethylsilanyl-ethoxy)3H-isobenzofuran-1-one

Product 1

HCID 59794521[6-Ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro isobenzofuran-5-yl]-acetaldehydeYield 69%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 6-allyl-5-ethyl-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one (261 mg, 0.788 mmol) in MeOH (5 mL), CH2Cl2 (5 mL) and pyridine (50 μL) was cooled to −78° C. using a dry ice/acetone bath according to the procedure of Smith, D. B. et al., J. Org. Chem., 1996, 61, 6, 2236. A stream of ozone was bubbled through the reaction via a gas dispersion tube until the reaction became blue in color (15 minutes). The ozone line was replaced with a stream of nitrogen and bubbling continued for another 15 minutes, by which time the blue color had disappeared. To this solution at −78° C. was added thiourea (59.9 mg, 0.788 mmol) in one portion, and the cooling bath was removed. The reaction was allowed to warm to room temperature and stirred for 15 hours. The reaction mixture was filtered and then partitioned between CH2Cl2 and water. The aqueous layer was extracted with CH2Cl2 one more time and the organic extracts were combined, washed with aqueous 1N HCl, saturated NaHCO3 and brine and dried over sodium sulfate. Filtration and evaporation of solvents in vacuo yielded the crude product, which was purified by silica gel chromatography to afford 181 mg (69%) of the product as a white solid. 1H NMR (300 MHz, CDCl3): δ=0.04 (s, 9H), 1.11 (t, J=7.5 Hz, 3H), 1.19 (m, 2H), 2.21 (s, 3H), 2.66 (q, J=7.5 Hz, 2H), 3.90 (s, 2H), 4.36 (m, 2H), 5.18 (s, 2H), 9.71 (s, 1H) ppm.

Workup

  1. customA stream of ozone was bubbled through the reaction via a gas dispersion tube until the reaction
  2. custombecame blue in color (15 minutes)
  3. custombubbling
  4. customthe cooling bath was removed
  5. filtrationThe reaction mixture was filtered
  6. custompartitioned between CH2Cl2 and water
  7. extractionThe aqueous layer was extracted with CH2Cl2 one more time
  8. washwashed with aqueous 1N HCl, saturated NaHCO3 and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationFiltration and evaporation of solvents in vacuo
  11. customyielded the crude product, which
  12. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-537bcbbb1804491386bd3971bd796bce
Source dataset
uspto-grants-2014_10
Patent number
US08871785B2

Linked notes

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