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 1781538Notes

Reaction equation

HRID 1781538 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:14][CH2:15][CH3:16])(=[O:13])[CH:10]([CH3:12])[CH3:11].[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]/[CH:38]=[C:39](\[CH3:42])/[CH2:40]Br.[NH4+].[Cl-]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C.C(Cl)Cl.CCOC(C)=O>[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](\[CH3:42])/[CH2:40][C:10]([CH3:12])([CH3:11])[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

8

Reactant 4

HCID 7342Ethyl isobutyrateHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 67019128(E)-4-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-2-methylbut-2-enyl bromide

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 3

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolventHCID 21226138Dichloromethane ethylacetateSolvent

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 mixture 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 Na2SO4 and evaporated to give a residue which was passed through a column (silica gel, CH2Cl2 -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 Na2SO4
  6. customevaporated
  7. customto give a residue which

Sources & evidence

ORD record
ord-8e444441d4214018adf3d389f94b601f
Source dataset
uspto-grants-1997_05
Patent number
US05633279

Reaction notes

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