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

HRID 32966Notes

Reaction equation

HRID 32966 reaction equation
COC(=O)CCC(C)=[CH:7][CH2:8][C:9]1[C:10]([O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21].N1C=CC=CC=1.NC(N)=S.C[OH:42]>C(Cl)Cl>[CH3:19][O:18][C:17]1[C:16]([CH3:20])=[C:15]2[C:11]([C:12](=[O:21])[O:13][CH2:14]2)=[C:10]([O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[C:9]=1[CH2:8][CH:7]=[O:42]

Participants

6

Reactant 4

HCID 887MethanolHCID 1049PyridineHCID 2723790ThioureaHCID 670105946-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic Acid Methyl Ester

Product 1

HCID 57478686[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-acetaldehydeYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid methyl ester (618 mg, 1.42 mmol) in MeOH (10 mL), CH2Cl2 (10 mL) and pyridine (50 μL, 0.618 mmol) was cooled to −70° 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, thiourea (75.7 mg, 0.994 mmol) was added in one portion at −70° C., and the cooling bath was removed. The reaction was allowed to warm to room temperature and stirred for 15 hours. The reaction was worked up by filtration to remove solid thiourea S-dioxide, and then partitioned between CH2Cl2 and water. The organic layer was removed. The aqueous layer was washed with CH2Cl2 one more time, and the organic extracts were combined. The organic layer was washed with aqueous 1N HCl, saturated NaHCO3 and brine. The organic extracts were dried in vacuo and the residue was purified to by silica gel chromatography to afford 357 mg (75%) of the product as a white solid. 1H NMR (300 MHz, CDCl3) δ-0.01 (s, 9H), 1.05-1.15 (m, 2H), 2.15 (s, 3H), 3.69 (s, 3H), 3.78 (d, 2H, J=1 Hz), 4.27-4.39 (m, 2H), 5.11 (s, 2H), 9.72 (d, 1H, J=1 Hz) 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 was worked up by filtration
  6. customto remove solid thiourea S-dioxide
  7. custompartitioned between CH2Cl2 and water
  8. customThe organic layer was removed
  9. washThe aqueous layer was washed with CH2Cl2 one more time
  10. washThe organic layer was washed with aqueous 1N HCl, saturated NaHCO3 and brine
  11. customThe organic extracts were dried in vacuo
  12. customthe residue was purified to by silica gel chromatography

Sources & evidence

ORD record
ord-f50cec52b4d0470893822494a8610be5
Source dataset
uspto-grants-2008_09
Patent number
US07427636B2

Reaction notes

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