Triethylamine → HCID 22843234, compound

HRID 1029924Notes

Reaction equation

HRID 1029924 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[C:21]1([C:27]2([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C@H:35]3[C@H:31]([CH2:32][NH:33][CH2:34]3)[C:30](=[O:36])[CH2:29][CH2:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11]([N:33]1[CH2:32][C@H:31]2[C@H:35]([C:27]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:28][CH2:29][C:30]2=[O:36])[CH2:34]1)=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7014956(S)-3-((tert-Butoxycarbonyl)amino)-2-phenylpropanoic acidHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride

Product 1

HCID 22843234HCID 22843234, compoundYield 74.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-Carbonyldiimidazole (0.5 g) is added to a solution of (S)-3-tert-butoxycarbonylamino-2-phenylpropionic acid (0.79 g) in dry dichloromethane (20 cc), cooled to +5° C. The mixture is stirred for 1 hour 15 minutes at +5° C. and a solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (1 g) and triethylamine (0.4 cc) in dichloromethane (25 cc) is then added. The reaction mixture is stirred for 15 minutes at +5° C. and then for 16 hours at 20° C. The reaction mixture is washed with distilled water (3×100 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 (0.2-0.06 mm, diameter 3 cm, height 30 cm), eluting with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting 50 cc fractions. Fractions 2 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa). (3aR,7aR)-2-[(S)-2-tert-butoxycarbonylaminomethyl-2-phenylacetyl]-7,7-diphenyl-4-perhydroisoindolone (1.2 g) is obtained in the form of a white meringue.

Workup

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred for 15 minutes at +5° C.
  3. waitfor 16 hours at 20° C
  4. washThe reaction mixture is washed with distilled water (3×100 cc)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is chromatographed on a silica gel column (0.2-0.06 mm, diameter 3 cm, height 30 cm)
  9. washeluting with a mixture of cyclohexane and ethyl acetate (50/50 by volume)
  10. customcollecting 50 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-dfb9f429c6034be9a9f7543ad82908f9
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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