Triethylamine → HCID 67915780, compound

HRID 1029938Notes

Reaction equation

HRID 1029938 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.[F:15][C:16]1[CH:17]=[C:18]([C:22]2([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=3)[CH:30]3[CH:26]([CH2:27][NH:28][CH2:29]3)[C:25](=[O:31])[CH2:24][CH2:23]2)[CH:19]=[CH:20][CH:21]=1.C(N(CC)CC)C>ClCCl>[F:38][C:34]1[CH:33]=[C:32]([C:22]2([C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([F:15])[CH:17]=3)[CH:30]3[CH:26]([CH2:27][NH:28][CH:29]3[C:10](=[O:12])[CH2:9][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[N:2]([CH3:1])[CH3:13])[C:25](=[O:31])[CH2:24][CH2:23]2)[CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 204661092-(2-(Dimethylamino)phenyl)acetic acidHCID 679158007,7-Bis(3-Fluorophenyl)-4-perhydroisoindolone hydrochloride

Product 1

HCID 67915780HCID 67915780, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

N,N'-carbonyldiimidazole (0.59 g) is added to a solution of (2-dimethylaminophenyl)acetic acid (0.65 g) in dry dichloromethane (20 cc) cooled to +4° C. The mixture is stirred for 90 minutes at 25° C. and a solution of 7,7-bis-(3-fluorophenyl)-4-perhydroisoindolone hydrochloride (1.3 g) and triethylamine (1.02 cc) in dry dichloromethane (25 cc) is then added dropwise. The reaction mixture is stirred for 16 hours at 25° C. and washed with water (2×250 cc) and with saturated sodium chloride solution (250 cc). The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 2.3 cm, height 23 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (55/45) and collecting 15 cc fractions. Fractions 6 to 18 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is solidified using isopropyl ether to give (3aRS,7aRS)-7,7-bis-(3-fluorophenyl)-2-(2-dimethylaminophenyl)acetyl-4-perhydroisoindolone (0.6 g), from which the hydrochloride is prepared by dissolving in ethyl acetate (1 cc) and adding a 3N solution of hydrochloric acid in isopropyl ether. The precipitate is drained, washed with isopropyl ether and dried. (3aRS,7aRS)-7,7-bis-(3-fluorophenyl)-2-(2-dimethylaminophenyl)acetyl-4-perhydroisoindolone hydrochloride (0.48 g) is obtained in the form of a white solid.

Workup

  1. temperaturecooled to +4° C
  2. stirringThe reaction mixture is stirred for 16 hours at 25° C.
  3. washwashed with water (2×250 cc) and with saturated sodium chloride solution (250 cc)
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.063 mm, diameter 2.3 cm, height 23 cm)
  7. washeluting under a nitrogen pressure of 0.5 bar
  8. additionwith a mixture of cyclohexane and ethyl acetate (55/45)
  9. customcollecting 15 cc fractions
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-8404917d02564a25a5c5c322da309e11
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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