Hydrochloric Acid → HCID 67810935, compound

HRID 1721208Notes

Reaction equation

HRID 1721208 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(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

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 682631,1'-CarbonyldiimidazoleHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 67809084HCID 67809084, compound

Product 1

HCID 67810935HCID 67810935, compoundYield 54.7%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent4×HCID 8471TriethylamineSolvent

Conditions

Temperature
4 °C

Procedure

0.17 g of carbonyldiimidazole is added to a solution, cooled to +4° C. of 0.19 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 0.35 g of (3aR, 7R,7aR)-7-chloro-4,4-diphenylperhydroisoindole hydrochloride in 10 cm3 of dry dichloromethane is added followed by a solution of 0.15 cm3 of triethylamine in 10 cm3 of dry dichloromethane. The reaction mixture is stirred at room temperature for 20 hours and then diluted with 120 cm3 of dichloromethane, washed with 80 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 2 cm, height 22 cm), eluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (75/25 by volume) and collecting fractions of 20 cm3. Fractions 6 to 9 are pooled and 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 25 cm3 of ethyl ether, followed by the addition of 5 cm3 of a 3.2N solution of hydrochloric acid in ethyl ether, washing with ethyl ether and drying. 0.14 g of (3aR, 7R,7aR)-7-chloro-2-[(2-dimethylaminophenyl)acetyl]-4,4diphenylperhydroisoindole hydrochloride is obtained in the form of white crystals; melting point 190° C.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 20 hours
  2. washwashed with 80 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 2 cm, height 22 cm)
  7. washeluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (75/25 by volume)
  8. customcollecting fractions of 20 cm3
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe product, which is obtained in the form of a base
  11. washwashing with ethyl ether
  12. customdrying

Sources & evidence

ORD record
ord-bcf0d0a94f3f46e092912477b098197d
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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