2-Methoxyphenylacetic acid → (3aR,7aR)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone

HRID 1196273Notes

Reaction equation

HRID 1196273 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:14]1([C:20]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:28]3[C@H:24]([CH2:25][NH:26][CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>ClCCl>[C:30]1([C:20]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C@H:28]3[C@H:24]([CH2:25][N:26]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 71342-Methoxyphenylacetic acidHCID 8471TriethylamineHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride

Product 1

HCID 15182925(3aR,7aR)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindoloneYield 64.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (1 g) is added to a solution, cooled to +5° C., of 2-methoxyphenylacetic acid (1 g) in dry dichloromethane (30 cc). The mixture is stirred for 40 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2 g) and triethylamine (1.7 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 1.8 cm, height 13 cm), eluting with ethyl acetate and collecting 25-cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc). The crystals are drained, washed with isopropyl ether (25 cc) and dried. (3aR,7aR)-(-)-7,7-Diphenyl-2-[(2-methoxyphenyl)acetyl]perhydro-4-isoindolone (1.7 g) is obtained in the form of white crystals, m.p. 200° C.; [α]D20 =-274° (c=0.49, acetic acid).

Workup

  1. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  2. washwashed with water (2×50 cc)
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (0.2-0.063 mm, diameter 1.8 cm, height 13 cm)
  7. washeluting with ethyl acetate
  8. customcollecting 25-cc fractions
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe residue is crystallized in a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc)
  11. washwashed with isopropyl ether (25 cc)
  12. customdried

Sources & evidence

ORD record
ord-8f752acfbcff416489595ba161b08ddc
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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