Ethyl Acetate → HCID 67661107, compound

HRID 55422Notes

Reaction equation

HRID 55422 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[Mg]Br.C([O:14][CH2:15][CH:16]1[CH2:24][CH:23]2[CH:19]([CH2:20][N:21]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:22]2)[C:18](=[O:32])[CH2:17]1)(=O)C.[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1>[CH2:25]([N:21]1[CH2:20][CH:19]2[CH:23]([CH2:24][CH:16]([CH2:15][OH:14])[CH2:17][C:18]2([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[OH:32])[CH2:22]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 18931543(3aRS,6SR,7aSR)-6-acetoxymethyl-2-benzyl-4-perhydroisoindoloneHCID 178489560HCID 178489560, compound

Product 1

HCID 67661107HCID 67661107, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

To a suspension of 2-methoxyphenylmagnesium bromide (prepared from 24.9 cm3 of 2-bromoanisole and 4.86 g of magnesium) in 200 cm3 of anhydrous tetrahydrofuran is added a solution of 8.0 g of (3aRS,6SR,7aSR)-6-acetoxymethyl-2-benzyl-4-perhydroisoindolone in 60 cm3 of anhydrous tetrahydrofuran. The reaction mixture is stirred for 20 hours at 20° C. and then cooled to +5° C. and treated with 120 cm3 of saturated aqueous ammonium chloride solution and 100 cm3 of ethyl acetate. After filtration of the mixture, the organic phase is washed with brine and then 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 0.06-0.200 mm, height 40 cm) in a mixture of 1,2-dichloroethane and methanol (95/5 by volume). After recrystallization in ethyl ether, 3.2 g of (3aRS,4RS,6SR, 7aSR)-2-benzyl-6-hydroxymethyl-4-(2-methoxyphenyl)-4-perhydroisoindolol are obtained, in the form of a white solid melting at 110° C.

Workup

  1. temperaturecooled to +5° C.
  2. filtrationAfter filtration of the mixture
  3. washthe organic phase is washed with brine
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (particle size 0.06-0.200 mm, height 40 cm) in a mixture of 1,2-dichloroethane and methanol (95/5 by volume)
  7. customAfter recrystallization in ethyl ether

Sources & evidence

ORD record
ord-204dd5be0eb74850b27ab41998e173e3
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Reaction notes

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