Triethylamine → (3aRS,7aRS)-2-[(2-dimethylamino-6-fluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone

HRID 1029903

반응식

HRID 1029903 반응식
[CH3:1][N:2]([CH3:14])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[CH2:10][C:11]([OH:13])=O.Cl.[C:16]1([C:22]2([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][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:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>ClCCl>[CH3:14][N:2]([CH3:1])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[CH2:10][C:11]([N:28]1[CH2:27][CH:26]2[CH:30]([C:22]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:23][CH2:24][C:25]2=[O:31])[CH2:29]1)=[O:13]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 19899901(2-Dimethylamino-6-fluorophenyl)acetic acidHCID 212645437,7-Diphenylhexahydro-1H-isoindol-4(2H)-one hydrochloride

생성물 1

HCID 67916077(3aRS,7aRS)-2-[(2-dimethylamino-6-fluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone수율 76.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

N,N'-Carbonyldiimidazole (1.62 g) is added to a solution of (2-dimethylamino-6-fluorophenyl)acetic acid (1.97 g) in dry dichloromethane (50 cc), cooled to +5° C. The mixture is stirred for 90 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (3.27 g) and triethylamine (2.8 cc) in dichloromethane (50 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×100 cc), dried over magnesium sulphate and filtered and the filtrate is 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 4 cm, height 25 cm), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (70/30 by volume) and collecting 50 cc fractions. Fractions 6 to 19 are combined and concentrated to dryness under reduced pressure. The residue is triturated in ethyl ether. The crystals are drained and dried. (3aRS,7aRS)-2-[(2-dimethylamino-6-fluorophenyl)acetyl]-7,7-diphenyl-4-perhydroisoindolone (3.6 g) is obtained in the form of white crystals melting at 210° C.

후처리

  1. temperaturecooled to +5° C
  2. stirringThe reaction mixture is stirred at 20° C. for 16 hours
  3. washwashed with water (2×100 cc)
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 4 cm, height 25 cm)
  8. washeluting under a nitrogen pressure of 0.5 bar
  9. additionwith a mixture of cyclohexane and ethyl acetate (70/30 by volume)
  10. customcollecting 50 cc fractions
  11. concentrationconcentrated to dryness under reduced pressure
  12. customThe residue is triturated in ethyl ether
  13. customdried

출처 및 근거

ORD 기록
ord-d33bb025c3a441839cbd379e11a03386
출처 데이터셋
uspto-grants-1992_04
특허 번호
US05102667

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