Triethylamine → (3aR,4S,7aR)-2-[(2-dimethylaminophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolol

HRID 2400010Notes

Reaction equation

HRID 2400010 reaction equation
[CH3:1][N:2]([CH3:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:15]1([C:21]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C@H:29]3[C@H:25]([CH2:26][NH:27][CH2:28]3)[C@@H:24]([OH:30])[CH2:23][CH2:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[CH3:13][N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([N:27]1[CH2:26][C@H:25]2[C@H:29]([C:21]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:22][CH2:23][C@@H:24]2[OH:30])[CH2:28]1)=[O:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 22856103(3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol hydrochloride

Product 1

HCID 22856096(3aR,4S,7aR)-2-[(2-dimethylaminophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindololYield 54.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.49 g of N,N'-carbonyldiimidazole is added to a solution of 0.52 g of 2-dimethylaminophenylacetic acid in 20 cm3 of dry dichloromethane. The mixture is stirred for 30 minutes at +5° C. and then a solution of 0.93 g of (3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol hydrochloride and 0.84 cm3 of triethylamine in 10 cm3 of dichloromethane, is added. The reaction mixture is stirred for 2 hours at +5° C. and then washed with 10 cm3 of water, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (0.04 mm-0.06 mm, diameter 2 cm, height 35 cm), eluting with ethyl acetate and collecting fractions of 30 cm3. Fractions 8 to 27 are pooled, concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallised-from a mixture of 4 cm3 of acetonitrile and 20 cm3 of ethyl ether. The crystals are drained and dried under reduced pressure (2.7 kPa). 0.70 g of (3aR,4S,7aR)-2-[(2-dimethylaminophenyl)-acetyl]-7,7-diphenyl-4-perhydroisoindolol is obtained in the form of a white solid; melting point 160° C., [α]D20 =-162° (c=0.5, methanol).

Workup

  1. stirringThe reaction mixture is stirred for 2 hours at +5° C.
  2. washwashed with 10 cm3 of water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue obtained
  7. customis chromatographed on a silica gel column (0.04 mm-0.06 mm, diameter 2 cm, height 35 cm)
  8. washeluting with ethyl acetate
  9. customcollecting fractions of 30 cm3
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. additionThe residue is crystallised-from a mixture of 4 cm3 of acetonitrile and 20 cm3 of ethyl ether
  12. customdried under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-ba938821874c438db43d09b79dc6a1dc
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

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