Ethyl isobutyrate → ethyl (E) 6-(4-methoxyethoxymethoxy-1,3-dihydro-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,2,4-trimethyl-4-hexenoate

HRID 2396632Notes

Reaction equation

HRID 2396632 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:14][CH2:15][CH3:16])(=[O:13])C(C)C.[CH3:17][O:18][C:19]1[C:27]([CH3:28])=[C:26]2[C:22]([C:23](=[O:29])[O:24][CH2:25]2)=[C:21]([O:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH3:36])[C:20]=1[CH2:37][CH2:38][CH:39]([CH3:54])[CH2:40][C@H:41]([CH3:53])[C:42](N1[C@H](C(C)C)COC1=O)=O.[NH4+].[Cl-]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[CH3:36][O:35][CH2:34][CH2:33][O:32][CH2:31][O:30][C:21]1[C:20]([CH2:37]/[CH:38]=[C:39](\[CH3:54])/[CH2:40][C:41]([CH3:53])([CH3:42])[C:9]([O:14][CH2:15][CH3:16])=[O:13])=[C:19]([O:18][CH3:17])[C:27]([CH3:28])=[C:26]2[C:22]=1[C:23](=[O:29])[O:24][CH2:25]2

Participants

7

Reactant 4

HCID 7342Ethyl isobutyrateHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 1317192673-[6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-(S),4-dimethylhexanoyl)-4-(R)-isopropyl-2-oxazolidinone

Product 1

HCID 131719268ethyl (E) 6-(4-methoxyethoxymethoxy-1,3-dihydro-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,2,4-trimethyl-4-hexenoateYield 74%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

A freshly prepared solution of lithium diisopropylamide (2.8 mmol/10 ml THF) was cooled to -78° C. and ethyl isobutyrate (0.75 ml) was added slowly. The solution was stirred at -78° C. for 40 minutes and then a solution of (E) 4-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-methylbut-2-enyl bromide (0.6 g) in THF (2 ml) and HMPA (1.5 ml) was added via syringe at such rate that the temperature was maintained below -60° C. After stirring for 30 minutes at -78° C., the mixure was poured onto 100 ml of a concentrated solution of NH4Cl. The organic and aqueous phases were separated and the aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over NaSO4 and evaporated to give a residue which was passed through a column (silica gel, CHCl2 --EtOAc 95:5) to afford 480 mg (74%) of ethyl (E) 6-(4-methoxyethoxymethoxy-1,3-dihydro-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2,2,4-trimethyl-4-hexenoate as a colorless oil.

Workup

  1. temperaturewas maintained below -60° C
  2. stirringAfter stirring for 30 minutes at -78° C.
  3. customThe organic and aqueous phases were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (2×50 ml)
  5. dry with materialThe combined organic layers were dried over NaSO4
  6. customevaporated
  7. customto give a residue which

Sources & evidence

ORD record
ord-e2c7a39239094797be9833c34eea9eeb
Source dataset
uspto-grants-1996_02
Patent number
US05493030

Reaction notes

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