Hydrochloric Acid → (3aR, 7S, 7aR)-7-chloro-2-[(2-dimethylaminophenyl)acetyl]-4,4-diphenylperhydroisoindole hydrochloride

HRID 2400001Notes

Reaction equation

HRID 2400001 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][N:14]([CH3:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][C:22]([OH:24])=O.Cl.[Cl:27][C@@H:28]1[C@@H:36]2[C@@H:32]([CH2:33][NH:34][CH2:35]2)[C:31]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:30][CH2:29]1.Cl>ClCCl.C(#N)C.C(OCC)C.C(N(CC)CC)C>[ClH:27].[Cl:27][C@@H:28]1[C@@H:36]2[C@@H:32]([CH2:33][N:34]([C:22](=[O:24])[CH2:21][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[N:14]([CH3:13])[CH3:25])[CH2:35]2)[C:31]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:30][CH2:29]1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 682631,1'-CarbonyldiimidazoleHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 67809337(3aR,7S,7aR)-7-chloro-4,4-diphenyl-perhydroisoindole hydrochloride

Product 1

HCID 67809116(3aR, 7S, 7aR)-7-chloro-2-[(2-dimethylaminophenyl)acetyl]-4,4-diphenylperhydroisoindole hydrochlorideYield 13%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent4×HCID 8471TriethylamineSolvent

Procedure

0.39 g of carbonyldiimidazole is added to a solution, cooled to +4° C., of 0.43 g of (2-dimethylaminophenyl)-acetic acid in 15 cm3 of dry dichloromethane. The mixture is stirred for one hour at +4° C. and then a solution of 0.84 g of (3aR,7S,7aR)-7-chloro-4,4-diphenylperhydro-isoindole hydrochloride in 10 cm3 of dry dichloromethane is then added followed by a solution of 0.34 cm3 of triethylamine in 10 cm3 of dry dichloromethane. The reaction mixture is stirred at room temperature for 20 hours and then diluted with 100 cm3 of dichloromethane, washed with 50 cm3 of water and then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 23 cm), eluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (25/75 by volume) and collecting fractions of 80 cm3. Fraction 2 is concentrated to dryness under reduced pressure (2.7 kPa). The product, which is obtained in the form of a base, is converted to the hydrochloride by dissolving in 4 cm3 of acetonitrile followed by the addition of 6 cm3 of a 3.2N solution of hydrochloric acid in ethyl ether, washing with isopropyl ether and drying. 0.08 g of (3aR,7S,7aR)-7-chloro-2-[(2-dimethylamino-phenyl)acetyl]-4,4-diphenylperhydroisoindole hydrochloride is obtained in the form of a beige solid.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 20 hours
  2. washwashed with 50 cm3 of water
  3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 23 cm)
  7. washeluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (25/75 by volume)
  8. customcollecting fractions of 80 cm3
  9. concentrationFraction 2 is concentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe product, which is obtained in the form of a base
  11. washwashing with isopropyl ether
  12. customdrying

Sources & evidence

ORD record
ord-736897aa3e0d476a902f8f77a6082a9a
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

Loading…