Diisopropylamine → 3-[6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-(S),4-dimethylhexanoyl)-4-(R)-isopropyl-2-oxazolidinone

HRID 2396630Notes

Reaction equation

HRID 2396630 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[CH:13]([C@@H:16]1[CH2:20][O:19][C:18](=[O:21])[N:17]1[C:22](=[O:25])[CH2:23][CH3:24])([CH3:15])[CH3:14].[CH3:26][O:27][C:28]1[C:36]([CH3:37])=[C:35]2[C:31]([C:32](=[O:38])[O:33][CH2:34]2)=[C:30]([O:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH3:45])[C:29]=1[CH2:46][CH:47]=[C:48](C)[CH2:49]CC(O)=O>CCCCCC.O1CCCC1>[CH3:26][O:27][C:28]1[C:36]([CH3:37])=[C:35]2[C:31]([C:32](=[O:38])[O:33][CH2:34]2)=[C:30]([O:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH3:45])[C:29]=1[CH2:46][CH2:47][CH:48]([CH3:49])[CH2:24][C@H:23]([CH3:1])[C:22]([N:17]1[C@H:16]([CH:13]([CH3:15])[CH3:14])[CH2:20][O:19][C:18]1=[O:21])=[O:25]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 643512(4R)-3-Propanoyl-4-(propan-2-yl)-1,3-oxazolidin-2-oneHCID 572018826-(1,3-Dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoic acidHCID 178418339Butyllithium

Product 1

HCID 1317192673-[6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-(S),4-dimethylhexanoyl)-4-(R)-isopropyl-2-oxazolidinone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1.38 molar n-butyllithium in hexane (11.8 ml) was added to diisopropylamine (2.45 ml) in tetrahydrofuran (50 ml) at -10° C. After 20 minutes, the solution was cooled to -78° C., and a solution of (R)-4-isopropyl-3-propionyl-2-oxazolidinone [prepared as described in J. Am. Chem. Soc., 103:2127 (1981)](3.23 g) in tetrahydrofuran (10 ml) was added. After 30 minutes (E) 4-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-methylbut-2-enyl bromide (2.54 g) in tetrahydrofuran (12 ml) was added. The reaction temperature was allowed to reach -10° C. slowly, then maintained at that temperature for 3 hours. The reaction was quenched with 10% aqueous ammonium chloride then extracted with ethyl acetate. The extract was washed with 10% hydrochloric acid, dilute aqueous sodium bicarbonate and water, then dried and evaporated. The residue was chromatographed on silica gel, eluting with 2:1 hexane:acetone, to yield (E) 3-[6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-(S),4-dimethylhexanoyl)-4-(R)-isopropyl-2-oxazolidinone as an oil.

Workup

  1. customto reach -10° C.
  2. temperaturemaintained at that temperature for 3 hours
  3. customThe reaction was quenched with 10% aqueous ammonium chloride
  4. extractionthen extracted with ethyl acetate
  5. washThe extract was washed with 10% hydrochloric acid, dilute aqueous sodium bicarbonate and water
  6. customdried
  7. customevaporated
  8. customThe residue was chromatographed on silica gel
  9. washeluting with 2:1 hexane

Sources & evidence

ORD record
ord-d19aba58ef604060a3a6aec56943a858
Source dataset
uspto-grants-1996_02
Patent number
US05493030

Reaction notes

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