Hydrochloric Acid → (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

HRID 2396636Notes

Reaction equation

HRID 2396636 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C)(C)C.C([Li])CCC.CCCCCC.[CH3:30][O:31][C:32]1[C:40]([CH3:41])=[C:39]2[C:35]([C:36](=[O:42])[O:37][CH2:38]2)=[C:34]([O:43]COCCOC)[C:33]=1[CH2:50][CH2:51][CH:52]([CH3:67])[CH2:53][C@H:54](C)[C:55](N1[C@H](C(C)C)COC1=O)=[O:56].Cl>O1CCCC1.C(OCC)(=O)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:55](=[O:56])[CH2:54][CH2:53]/[C:52](/[CH3:67])=[CH:51]/[CH2:50][C:33]1[C:34]([OH:43])=[C:35]2[C:39](=[C:40]([CH3:41])[C:32]=1[O:31][CH3:30])[CH2:38][O:37][C:36]2=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8058HexaneHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 1317192673-[6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-(S),4-dimethylhexanoyl)-4-(R)-isopropyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 70300567(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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-4-benzyl-2-oxazolidinone (177.4 g, 1 mol) and t-butyl alcohol (74.1 g , 1 mol) in anhydrous tetrahydrofuran (2 L) was cooled to -78° C. A 1.6M solution of n-butyllithium in hexane (1280 mL, 2 mol) was added maintaining a temperature below -30° C. After recooling to -78° C. the (E) 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoyl chloride solution (1 mol) was added and the mixture was allowed to warm to 0° C. over 2 hours. 2N Hydrochloric acid (1.5 L) and ethyl acetate (1 L) were added. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate (0.5 L), 2N hydrochloric acid (0.5 L), and brine (1 L). After drying over sodium sulfate, the organic layer was evaporated at reduced pressure to leave the crude imide as a tan solid. Recrystallization from ethyl acetate/hexane (2.5 L/2.5 L) gave (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 as off-white, shiny plates, m.p. 112°-113° C.

Workup

  1. temperaturemaintaining a temperature below -30° C
  2. customAfter recooling to -78° C.
  3. additionwas added
  4. washThe organic layer was washed sequentially with saturated aqueous sodium bicarbonate (0.5 L), 2N hydrochloric acid (0.5 L), and brine (1 L)
  5. dry with materialAfter drying over sodium sulfate
  6. customthe organic layer was evaporated at reduced pressure
  7. customto leave the crude imide as a tan solid
  8. customRecrystallization from ethyl acetate/hexane (2.5 L/2.5 L)

Sources & evidence

ORD record
ord-0cbb144f4d5944e18d961ac742363679
Source dataset
uspto-grants-1996_02
Patent number
US05493030

Reaction notes

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