Dicyclohexylcarbodiimide → (3aR,7aR)-7,7-diphenyl-2-[(S)-2-methoxy-2-phenylacetyl]-4-perhydroisoindolone

HRID 1029925Notes

Reaction equation

HRID 1029925 reaction equation
O.OC1C2N=NNC=2C=CC=1.[CH3:12][O:13][C@@H:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:15]([OH:17])=O.C1(N=C=NC2CCCCC2)CCCCC1.Cl.[C:40]1([C:46]2([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[C@H:54]3[C@H:50]([CH2:51][NH:52][CH2:53]3)[C:49](=[O:55])[CH2:48][CH2:47]2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[C:56]1([C:46]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C@H:54]3[C@H:50]([CH2:51][N:52]([C:15](=[O:17])[C@@H:14]([O:13][CH3:12])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:53]3)[C:49](=[O:55])[CH2:48][CH2:47]2)[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 643325(+)-Methoxyphenylacetic acidHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 22843244(3aR,7aR)-7,7-diphenyl-2-[(S)-2-methoxy-2-phenylacetyl]-4-perhydroisoindoloneYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Hydroxybenzotriazole monohydrate (1 g) is added to a solution of (S)-α-methoxyphenylacetic acid (1.23 g) in dry dimethylformamide (20 cc), cooled to +5° C.; stirring is continued for 15 minutes and N,N'-dicyclohexylcarbodiimide (1.53 g) is then added. The mixture is stirred for 1 hour at +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.43 g) and diisopropylethylamine (1.28 cc) in dry dimethylformamide (10 cc) is then added. The reaction mixture is stirred at +5° C. for 2 hours and then at ambient temperature for 2 hours. The reaction mixture, taken up in ethyl acetate (100 cc), is filtered; the filtrate is washed with distilled water (2×100 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (diameter 2.2 cm, height 27 cm), eluting with a mixture of cyclohexane and ethyl acetate (80/20 by volume) and collecting 20 cc fractions. Fractions 68 to 177 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from isopropyl ether (15 cc); the crystals obtained are drained and then dried. (3aR,7aR)-7,7-diphenyl-2-[(S)-2-methoxy-2-phenylacetyl]-4-perhydroisoindolone (1.3 g) is obtained in the form of white crystals melting at 130° C.; [α]D20 =-230° (c=1, methanol).

Workup

  1. temperaturecooled to +5° C.
  2. stirringThe mixture is stirred for 1 hour at +5° C.
  3. stirringThe reaction mixture is stirred at +5° C. for 2 hours
  4. waitat ambient temperature for 2 hours
  5. filtrationis filtered
  6. washthe filtrate is washed with distilled water (2×100 cc)
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe residue is chromatographed on a silica gel column (diameter 2.2 cm, height 27 cm)
  11. washeluting with a mixture of cyclohexane and ethyl acetate (80/20 by volume)
  12. customcollecting 20 cc fractions
  13. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  14. customThe residue is crystallized from isopropyl ether (15 cc)
  15. customthe crystals obtained
  16. customdried

Sources & evidence

ORD record
ord-4efdaf62ebd443b5a7c8bfa101812426
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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