Water → (3aRS,4RS,7aSR)-2-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-4-perhydroisoindolol

HRID 55438

Reaction equation

HRID 55438 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C([Li])CCC.[CH2:21]([N:28]1[CH2:36][CH:35]2[CH:30]([CH2:31][CH2:32][CH2:33][C:34]2=[O:37])[CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O>O1CCCC1.CCCCCC>[CH2:21]([N:28]1[CH2:36][CH:35]2[CH:30]([CH2:31][CH2:32][CH2:33][C:34]2([C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:14])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=2)[OH:37])[CH2:29]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 438112032-Benzyloctahydro-4H-isoindol-4-oneHCID 178418339Butyllithium

Product 1

HCID 86750777(3aRS,4RS,7aSR)-2-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-4-perhydroisoindolol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3.06 cm3 of 3,5bis(trifluoromethyl)bromobenzene in 15 cm3 of dry tetrahydrofuran is added, at -78° C., a solution of 10.9 cm3 of 1.6M butyllithium in hexane. This solution is stirred for 30 minutes at -78° C., and a solution of 1 g of (3aRS,7aSR)-2-benzyl-4-perhydroisoindolone in 5 cm3 of tetrahydrofuran is then run in dropwise. The reaction mixture is subsequently stirred at room temperature for 18 hours, treated with 20 cm3 of water and then extracted with 20 cm3 of ethyl acetate. The organic phase is separated out after settling has taken place, washed with twice 20 cm3 of water, then with 20 cm3 of saturated sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 2 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (90/10 by volume) and collecting 20 cm3 fractions. Fractions 26 to 37 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.82 g of (3aRS,4RS,7aSR)-2-benzyl-4-[3,5-bis(trifluoromethyl)phenyl]-4-perhydroisoindolol is obtained in the form of an oil.

Workup

  1. stirringThe reaction mixture is subsequently stirred at room temperature for 18 hours
  2. extractionextracted with 20 cm3 of ethyl acetate
  3. customThe organic phase is separated out after settling
  4. washwashed with twice 20 cm3 of water
  5. dry with materialwith 20 cm3 of saturated sodium chloride solution, dried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 2 cm, height 20 cm)
  8. washeluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (90/10 by volume)
  9. customcollecting 20 cm3 fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-7592297c535b442e849e58d808d9c1d9
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Linked notes

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