Triphenylphosphine → 4-[1-[4-(2-Chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-benzonitrile

HRID 896740Notes

Reaction equation

HRID 896740 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH:13]([NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1)[C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([O:21][CH3:22])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:51][CH2:52][C@H:53]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)O.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:51][CH2:52][CH:53]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[O:20][C:17]1[CH:18]=[CH:19][C:14]([CH:13]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([C:28]#[N:29])=[CH:30][CH:31]=2)[CH2:12][N:3]2[C:4](=[O:11])[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])=[CH:15][C:16]=1[O:21][CH3:22]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 6433232-Chloro-1-phenylethanol, (+)-HCID 5462977Diethyl azodicarboxylateHCID 228904554-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-1-(4-hydroxy-3-methoxy-phenyl)-ethyl amino]-benzonitrile

Product 1

HCID 228904504-[1-[4-(2-Chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-benzonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-1-(4-hydroxy-3-methoxy-phenyl)-ethylamino]-benzonitrile (1 g, 2.43 mmoles) was dissolved in tetrahydrofuran (30 ml) and triphenylphosphine (1.27 g, 4.84 mmoles), (S)-2-chloro-1-phenyl-ethanol (1.13 g, 7.26 mmoles) added. The reaction was cooled to 0° C. and diethylazodicarboxylate (0.842 g, 4.8 mmoles) added. The reaction temperature was allowed to come to room temperature and the reaction stirred for 2.5 hours. The solvent was removed in vacuo and the residue taken up in ethyl acetate, washed with 0.5 N sodium hydroxide several times, washed once with brine and dried over anhydrous sodium sulfate. The crude product was purified by flash chromatography on silica gel (30% ethyl acetate in hexanes) to yield 1.1 g of 4-[1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-benzonitrile, (82%).

Workup

  1. customto come to room temperature
  2. customThe solvent was removed in vacuo
  3. washwashed with 0.5 N sodium hydroxide several times
  4. washwashed once with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe crude product was purified by flash chromatography on silica gel (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-ef3beae37035432792a5989c068ef2d6
Source dataset
uspto-grants-2005_07
Patent number
US06919369B2

Reaction notes

Loading…