Ethyl Acetate → HCID 67661107, compound

HRID 1599128Notes

Reaction equation

HRID 1599128 reaction equation
C([O:4][CH2:5][CH:6]1[CH2:14][CH:13]2[CH:9]([CH2:10][N:11]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12]2)[C:8](=[O:22])[CH2:7]1)(=O)C.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Mg]Br.[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1>[CH2:15]([N:11]1[CH2:10][CH:9]2[CH:13]([CH2:14][CH:6]([CH2:5][OH:4])[CH2:7][C:8]2([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[O:24][CH3:23])[OH:22])[CH2:12]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=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

A solution of 8.0 g of (3aRS,6SR,7aSR)-6-acetoxymethyl-2-benzylperhydroisoindol-4-one in 60 cm3 of anhydrous tetrahydrofuran is added 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. The reaction mixture is stirred at 20° C. for 20 hours, 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, then dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.06-0.20 mm, height 40 cm) in a mixture of 1,2-dichloroethane and methanol (95:5 by volume). Recrystallization from ethyl ether gives 3.2 g of (3aRS,4RS,6SR,7aSR)-2-benzyl-6-hydroxymethyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol 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 silica gel column (particle size 0.06-0.20 mm, height 40 cm) in a mixture of 1,2-dichloroethane and methanol (95:5 by volume)
  7. customRecrystallization from ethyl ether

Sources & evidence

ORD record
ord-cc7e2bad72ea40a5867fa05124a0a9fb
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

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