3-(3-(1,3-Dioxoisoindolin-2-yl)propyl)benzaldehyde → (E)-2-(3-(3-(2-trifluoromethylstyryl)phenyl)propyl)isoindoline-1,3-dione

HRID 628622Notes

Reaction equation

HRID 628622 reaction equation
[Br-].[F:2][C:3]([F:31])([F:30])[C:4]1[CH:29]=[CH:28][CH:27]=[CH:26][C:5]=1[CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[O:32]=[C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35](=[O:42])[N:34]1[CH2:43][CH2:44][CH2:45][C:46]1[CH:47]=[C:48]([CH:51]=[CH:52][CH:53]=1)[CH:49]=O>>[F:31][C:3]([F:2])([F:30])[C:4]1[CH:29]=[CH:28][CH:27]=[CH:26][C:5]=1/[CH:6]=[CH:49]/[C:48]1[CH:47]=[C:46]([CH2:45][CH2:44][CH2:43][N:34]2[C:35](=[O:42])[C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:33]2=[O:32])[CH:53]=[CH:52][CH:51]=1.[F:31][C:3]([F:2])([F:30])[C:4]1[CH:29]=[CH:28][CH:27]=[CH:26][C:5]=1/[CH:6]=[CH:49]\[C:48]1[CH:47]=[C:46]([CH2:45][CH2:44][CH2:43][N:34]2[C:35](=[O:42])[C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:33]2=[O:32])[CH:53]=[CH:52][CH:51]=1

Participants

4

Reactant 2

HCID 577664653-(3-(1,3-Dioxoisoindolin-2-yl)propyl)benzaldehydeHCID 861853592-Trifluoromethylbenzyltriphenylphosphonium bromide

Product 2

HCID 68942028(E)-2-(3-(3-(2-trifluoromethylstyryl)phenyl)propyl)isoindoline-1,3-dioneHCID 68942117(Z)-2-(3-(3-(2-trifluoromethylstyryl)phenyl)propyl)isoindoline-1,3-dione

Procedure

2-Trifluoromethylbenzyltriphenylphosphonium bromide was coupled with phthalimide 29 following the method used in Example 44 except that the reaction was conducted at −78° C. instead of 0° C. before warming to room temperature. Purification by flash chromatography (10 to 40% EtOAc-hexanes gradient) gave (E)-2-(3-(3-(2-trifluoromethylstyryl)phenyl)propyl)isoindoline-1,3-dione (0.0797 g, trans-/cis-isomer ratio 15.6:1) as an oil and (Z)-2-(3-(3-(2-trifluoromethylstyryl)phenyl)propyl)isoindoline-1,3-dione (0.1139 g, trans-/cis-isomer ratio 8.1:1) as an oil. Yield (0.1936 g total, 83%): Trans-isomer: 1H NMR (400 MHz, CDCl3) δ 7.69-7.73 (m, 2H), 7.68 (d, J=7.6 Hz, 1H), 7.56-7.63 (m, 3H), 7.45 (t, J=7.6 Hz, 1H), 7.34 (dq, J=16.0, 2.0 Hz, 1H), 7.21-7.28 (m, 3H), 7.14-7.19 (m, 1H), 7.05 (d, J=7.6 Hz, 1H), 6.93 (d, J=16.4 Hz, 1H), 3.69 (t, J=7.2 Hz, 2H), 2.64 (t, J=7.2 Hz, 2H), 1.95-2.04 (m, 2H).

Workup

  1. customwas conducted at −78° C. instead of 0° C.
  2. customPurification by flash chromatography (10 to 40% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-7516fc5d91c3496aa7ae02163e5021a5
Source dataset
uspto-grants-2016_04
Patent number
US09314467B2

Reaction notes

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