HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Triethylamine → (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[(2-dimethylaminophenyl)acetyl]perhydro-4-isoindolone

HRID 1196288
Notes
Print preview

Reaction equation

HRID 1196288 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][N:28]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[N:2]([CH3:1])[CH3:13])[CH2:29]3)[C:25](=[O:31])[CH2:24][CH2:23]2)[CH:37]=[CH:36][CH:35]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

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

Product 1

HCID 67916096(3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[(2-dimethylaminophenyl)acetyl]perhydro-4-isoindoloneYield 34.4%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent
2×

Conditions

Temperature
25 °C

Procedure

N,N'-Carbonyldiimidazole (0.59 g) is added to a solution, cooled to +4° C., of (2-dimethylaminophenyl)acetic acid (0.65 g) in dry dichloromethane (20 cc). The mixture is stirred for 90 minutes at 25° C. and a solution of 7,7-bis(3-fluorophenyl)perhydro-4-isoindolone 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 column of silica gel (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 with isopropyl ether to give (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[(2-dimethylaminophenyl)acetyl]perhydro-4-isoindolone (0.6 g), the hydrochloride of which is prepared by dissolution in ethyl acetate (1 cc) and the addition of 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]perhydro-4-isoindolone hydrochloride (0.48 g) is obtained in the form of a white solid.

Workup

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

Sources & evidence

ORD record
ord-5dd6bb0bcaa24012a0e6b48eb824d8b3
Source dataset
uspto-grants-1992_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05112988

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes