Potassium Carbonate → (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[1-imino-2-(2-methoxyphenyl)ethyl]perhydro-4-isoindolone

HRID 1196287Notes

Reaction equation

HRID 1196287 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([NH2:12])=O.F[B-](F)(F)F.C([O+](CC)CC)C.Cl.[F:26][C:27]1[CH:28]=[C:29]([C:33]2([C:43]3[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=3)[CH:41]3[CH:37]([CH2:38][NH:39][CH2:40]3)[C:36](=[O:42])[CH2:35][CH2:34]2)[CH:30]=[CH:31][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(N(CC)CC)C>[F:49][C:45]1[CH:44]=[C:43]([C:33]2([C:29]3[CH:30]=[CH:31][CH:32]=[C:27]([F:26])[CH:28]=3)[CH:41]3[CH:37]([CH2:38][N:39]([C:10](=[NH:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:40]3)[C:36](=[O:42])[CH2:35][CH2:34]2)[CH:48]=[CH:47][CH:46]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 806622-(2-Methoxyphenyl)acetamideHCID 2723982Triethyloxonium tetrafluoroborateHCID 679158007,7-Bis(3-Fluorophenyl)-4-perhydroisoindolone hydrochloride

Product 1

HCID 67915925(3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[1-imino-2-(2-methoxyphenyl)ethyl]perhydro-4-isoindoloneYield 27.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of (2-methoxyphenyl)acetamide (0.9 g) in dry dichloromethane (3 cc) is treated with triethyloxonium tetrafluoroborate (1.14 g), and the solution obtained stirred for 20 hours at 25° C. After cooling to 0° C., a solution of 7,7-bis(3-fluorophenyl)perhydro-4-isoindolone hydrochloride (1.5 g) and triethylamine (1.4 cc) in dichloromethane (9 cc) is added to the reaction medium. The reaction mixture is stirred for 30 minutes at 25° C., then heated to reflux for 5 hours and finally stirred for a further 16 hours at 25° C. Saturated potassium carbonate solution (50 cc) is added, the mixture is stirred and filtered and the organic phase is washed with water (2×50 cc). After drying over magnesium sulphate, filtration and concentration to dryness under reduced pressure (2.7 kPa), the residue is chromatographed on a column of alumina (diameter 2.6 cm, height 24 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of 1,2 -dichloroethane and methanol (95:5 by volume) and collecting 15-cc fractions. Fractions 7 to 25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give (3aRS,7aRS)-7,7-bis(3-fluorophenyl)-2-[1-imino-2-(2-methoxyphenyl)ethyl]perhydro-4-isoindolone (0.54 g) in the form of a pale yellow meringue-like product.

Workup

  1. customthe solution obtained
  2. temperatureAfter cooling to 0° C.
  3. stirringThe reaction mixture is stirred for 30 minutes at 25° C.
  4. temperatureheated
  5. temperatureto reflux for 5 hours
  6. stirringfinally stirred for a further 16 hours at 25° C
  7. stirringthe mixture is stirred
  8. filtrationfiltered
  9. washthe organic phase is washed with water (2×50 cc)
  10. dry with materialAfter drying over magnesium sulphate, filtration and concentration to dryness under reduced pressure (2.7 kPa)
  11. customthe residue is chromatographed on a column of alumina (diameter 2.6 cm, height 24 cm)
  12. washeluting under a nitrogen pressure of 0.5 bar
  13. additionwith a mixture of 1,2 -dichloroethane and methanol (95:5 by volume)
  14. customcollecting 15-cc fractions
  15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-c70822ed882f42ccb98621dae89719c0
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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