Hydrochloric Acid → (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochloride

HRID 55433Notes

Reaction equation

HRID 55433 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@:9]1([OH:19])[CH2:17][C@H:16]([CH3:18])[CH2:15][C@@H:14]2[C@H:10]1[CH2:11][NH:12][CH2:13]2.[CH3:20][N:21]([CH3:32])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][C:29](O)=[O:30].O.ON1C2C=CC=CC=2N=N1.[ClH:44].CN(C)CCCN=C=NCC.Cl>ClCCl.O1CCOCC1.C(N(CC)CC)C>[ClH:44].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@:9]1([OH:19])[CH2:17][C@H:16]([CH3:18])[CH2:15][C@@H:14]2[C@H:10]1[CH2:11][N:12]([C:29](=[O:30])[CH2:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[N:21]([CH3:32])[CH3:20])[CH2:13]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 22872292(3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol

Product 1

HCID 22872290(3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochlorideYield 61.2%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol in 100 cm3 of dichloromethane are added 1.5 cm3 of triethylamine. The reaction mixture is cooled to 5° C. and 0.60 g of (2-dimethylaminophenyl)acetic acid, 0.10 g of 1-hydroxybenzotriazole monohydrate and 0.70 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added. The reaction mixture is maintained at 5° C. for 1 hour and at 20° C. for 16 hours and is then washed twice with 100 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm), eluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol (97/3 by volume) and collecting 50 cm3 fractions. Fractions 14 to 19 are concentrated and, after drying at 40° C. and at 15 Pa, 1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisonindolol is obtained, in the form of a white powder which is dissolved in 50 cm3 of dioxane. 3 cm3 of 5M hydrochloric acid solution are added to the dioxane and, after 1 hour at room temperature, the solution is concentrated under reduced pressure (2.7 kPa), stirred in isopropyl ether, filtered and dried at 40° C. under 15 Pa. 0.94 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochloride is obtained.

Workup

  1. temperatureThe reaction mixture is maintained at 5° C. for 1 hour and at 20° C. for 16 hours
  2. washis then washed twice with 100 cm3 of water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm)
  7. washeluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol (97/3 by volume)
  8. customcollecting 50 cm3 fractions
  9. concentrationFractions 14 to 19 are concentrated
  10. customafter drying at 40° C. and at 15 Pa
  11. custom1.0 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisonindolol is obtained, in the form of a white powder which
  12. concentrationthe solution is concentrated under reduced pressure (2.7 kPa)
  13. filtrationfiltered
  14. customdried at 40° C. under 15 Pa

Sources & evidence

ORD record
ord-531eb2fcf7c042828bacf0ea4c48b629
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Reaction notes

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