Triethylamine → HCID 67916214, compound

HRID 1196277Notes

Reaction equation

HRID 1196277 reaction equation
[C:1]([O:5][C:6]([N:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([OH:19])=O)[CH3:9])=[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)[CH:35]3[CH: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]([N:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([N:33]1[CH2:32][CH:31]2[CH: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:19])[CH3:9])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochlorideHCID 54108350HCID 54108350, compound

Product 1

HCID 67916214HCID 67916214, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N'-carbonyldiimidazole (1.13 g) is added to a solution, cooled to +5° C., of [2-(N-tert-butoxycarbonyl-N-methylamino)phenyl]acetic acid (1.85 g) in dry dichloromethane (30 cc). The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenylperhydro-4-isoindolone hydrochloride (2.29 g) and triethylamine (1.9 cc) in dichloromethane (20 cc) is then added. The reaction mixture is stirred at 20° C. for 2 hours, then washed with water (2×200 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 4 cm, height 50 cm), eluting under a nitrogen pressure of 0.7 bar with a mixture of cyclohexane and ethyl acetate (30:70 by volume) and collecting 125-cc fractions. Fractions 22 to 34 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-2-{[2-(N-tert-butoxycarbonyl-N-methylamino)phenyl]acetyl}-7,7-diphenylperhydro-4-isoindolone (2.8 g) in the form of a white meringue-like product.

Workup

  1. stirringThe reaction mixture is stirred at 20° C. for 2 hours
  2. washwashed with water (2×200 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 4 cm, height 50 cm)
  7. washeluting under a nitrogen pressure of 0.7 bar
  8. additionwith a mixture of cyclohexane and ethyl acetate (30:70 by volume)
  9. customcollecting 125-cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-58c39b56d0d54e8e9d03257bbc637189
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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