Acetic Acid → Ethyl 2-[3-(4-ethoxycarbonylphenoxy)propyl]-4,5,6,7-tetramethoxy-1-oxo-2-indancarboxylate

HRID 2268485Notes

Reaction equation

HRID 2268485 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH3:11])[C:5]([O:12][CH3:13])=[C:4]([O:14][CH3:15])[C:3]=1[CH2:16][C:17]([C:38]([O:40][CH2:41][CH3:42])=[O:39])([CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:29][CH:28]=1)[C:18]([O:20]CC)=O.C([Li])CCC.C(O)(=O)C>C1COCC1.CCCCCC.C(OCC)(=O)C>[CH2:36]([O:35][C:33]([C:30]1[CH:31]=[CH:32][C:27]([O:26][CH2:25][CH2:24][CH2:23][C:17]2([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:16][C:3]3[C:2](=[C:7]([O:8][CH3:9])[C:6]([O:10][CH3:11])=[C:5]([O:12][CH3:13])[C:4]=3[O:14][CH3:15])[C:18]2=[O:20])=[CH:28][CH:29]=1)=[O:34])[CH3:37]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 18348578Ethyl 3-(2-bromo-3,4,5,6-tetramethoxyphenyl)-2-ethoxycarbonyl-2-[3-(4-ethoxycarbonylphenoxy)propyl]propionateHCID 178418339Butyllithium

Product 1

HCID 18348506Ethyl 2-[3-(4-ethoxycarbonylphenoxy)propyl]-4,5,6,7-tetramethoxy-1-oxo-2-indancarboxylateYield 91.7%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 3-(2-bromo-3,4,5,6-tetramethoxyphenyl)-2-ethoxycarbonyl-2-[3-(4-ethoxycarbonylphenoxy)propyl]propionate (40.0 g) in THF (400 ml) was dropwise added n-butyl lithium in hexane (1.68M; 41.8 ml) under nitrogen atmosphere at −100° C. or under and the solution was allowed to warm to −78° C. in 30 min. The reaction mixture was cooled to −100° C. again and a solution of acetic acid (7.33 g) in THF (20 ml) was dropwise added, which was then allowed to warm to room temperature. The reaction mixture was diluted with ethyl acetate and the organic layer was washed with saturated aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride, and dried. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=7:1) to yield the entitled compound (29.7 g) as an oil.

Workup

  1. customat −100° C.
  2. temperatureThe reaction mixture was cooled to −100° C. again
  3. temperatureto warm to room temperature
  4. washthe organic layer was washed with saturated aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride
  5. customdried
  6. customThe solvent was removed in vacuo
  7. customThe residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=7:1)

Sources & evidence

ORD record
ord-0db50c41e4924a62b6bd274f4baca644
Source dataset
uspto-grants-2001_12
Patent number
US06326369B1

Reaction notes

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