Dihydrobenzofuran → 4-(2,3-Dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester

HRID 400615Notes

Reaction equation

HRID 400615 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]([OH:14])([C:10]([F:13])([F:12])[F:11])[CH2:6][C:7]([CH3:9])=[CH2:8])[CH3:2].[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH2:18][CH2:17]1.[Al+3].[Cl-].[Cl-].[Cl-]>ClC(Cl)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]([OH:14])([C:10]([F:13])([F:12])[F:11])[CH2:6][C:7]([C:21]1[C:20]2[O:16][CH2:17][CH2:18][C:19]=2[CH:24]=[CH:23][CH:22]=1)([CH3:9])[CH3:8])[CH3:2]

Participants

5

Reactant 3

HCID 10329DihydrobenzofuranHCID 6451240Aluminum(III) ChlorideHCID 17935595Ethyl 2-hydroxy-4-methyl-2-(trifluoromethyl)pent-4-enoate

Product 1

HCID 469391194-(2,3-Dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoic acid ethyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 2-hydroxy-4-methyl-2-trifluoromethylpent-4-enoic acid ethyl ester (100 g, 442 mmol) and 2,3-dihydrobenzofuran (57.7 g, 480 mmol) in 500 mL of dichloroethane was treated with AlCl3 (87.8 g, 660 mmol) while maintaining the internal temperature below 10° C. The reaction was allowed to warm to room temperature overnight and quenched with 1 L of cold 1 N HCl. The mixture was then extracted with three 1 L portions of ethyl acetate. The combined organic layers were washed with 1 L of saturated aqueous sodium bicarbonate solution, 1 L of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified on SiO2 (10% diethyl ether in hexanes). The resulting solid was recrystallized in hot hexanes to afford 39.5 g of 4-(2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester as a white solid (26% yield).

Workup

  1. temperaturewhile maintaining the internal temperature below 10° C
  2. customquenched with 1 L of cold 1 N HCl
  3. extractionThe mixture was then extracted with three 1 L portions of ethyl acetate
  4. washThe combined organic layers were washed with 1 L of saturated aqueous sodium bicarbonate solution, 1 L of brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on SiO2 (10% diethyl ether in hexanes)
  9. customThe resulting solid was recrystallized in hot hexanes

Sources & evidence

ORD record
ord-5214822b084445408d13ae6e3686e3fc
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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