Hydrochloric Acid → 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,4-dimethyl-4-hexenoyl]-2-oxazolidinone

HRID 1781547Notes

Reaction equation

HRID 1781547 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([CH:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:45])[CH2:25][CH2:26]/[C:27](/[CH3:44])=[CH:28]/[CH2:29][C:30]1[C:31]([OH:43])=[C:32]2[C:36](=[C:37]([CH3:41])[C:38]=1[O:39][CH3:40])[CH2:35][O:34][C:33]2=[O:42])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.I[CH3:47].Cl>O1CCCC1>[CH2:11]([CH:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:45])[CH2:25][CH2:26]/[C:27](/[CH3:44])=[CH:28]/[CH2:29][C:30]1[C:31]([OH:43])=[C:32]2[C:36](=[C:37]([CH3:41])[C:38]=1[O:39][CH3:40])[CH2:35][O:34][C:33]2=[O:42])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1.[CH2:11]([CH:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:45])[CH:25]([CH3:47])[CH2:26]/[C:27](/[CH3:44])=[CH:28]/[CH2:29][C:30]1[C:31]([OH:43])=[C:32]2[C:36](=[C:37]([CH3:41])[C:38]=1[O:39][CH3:40])[CH2:35][O:34][C:33]2=[O:42])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 683826924-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoyl]-2-oxazolidinone

Product 2

HCID 677716174-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,4-dimethyl-4-hexenoyl]-2-oxazolidinoneHCID 683826924-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoyl]-2-oxazolidinone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A 1M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (0.43L, 0.43 mol) was cooled to -78° C. and treated dropwise with a precooled solution of (S) 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoyl]-2-oxazolidinone (86 g, 0.179 mol) in tetrahydrofuran (250 mL), maintaining a temperature below -65° C. After 15 minutes stirring, iodomethane (56 mL, 0.9 mol) was added and the solution was warmed to -30° C. After 1 hour, the solution was warmed to 0° C. and 2N hydrochloric acid (0.4L) was added. The organic layer was washed with 2% sodium sulfite (0.2L) and brine (0.2L) and dried over sodium sulfate. After filtration, the volatiles were distilled at reduced pressure and the residue was applied to a bed of silica gel (0.45 kg). Elution with 40% ethyl acetate/hexane (4L) and concentration of the eluent gave the alkylation product (S) 4-benzyl-3-[(E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -2,4-dimethyl-4-hexenoyl]-2-oxazolidinone as a white foam. The product consisted of an 85:13 mixture of diastereomers at the 2-hexenoyl position.

Workup

  1. temperaturemaintaining a temperature below -65° C
  2. waitAfter 1 hour
  3. temperaturethe solution was warmed to 0° C.
  4. washThe organic layer was washed with 2% sodium sulfite (0.2L) and brine (0.2L)
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration
  7. distillationthe volatiles were distilled at reduced pressure
  8. washElution with 40% ethyl acetate/hexane (4L) and concentration of the eluent

Sources & evidence

ORD record
ord-a76e7895a60a43e49f3e09dc222840eb
Source dataset
uspto-grants-1997_05
Patent number
US05633279

Reaction notes

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