Triphenylphosphine → HCID 25014965, compound

HRID 1915141Notes

Reaction equation

HRID 1915141 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:24][OH:25].CC(OC(/N=N/C(OC(C)C)=O)=O)C.[O:44]=[C:45]1[CH:50]([N:51]2[C:59](=[O:60])[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][C:57]=3O)[C:52]2=[O:62])[CH2:49][CH2:48][C:47](=[O:63])[NH:46]1>C1COCC1>[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:24][O:25][C:54]1[CH:55]=[CH:56][CH:57]=[C:58]2[C:53]=1[C:52](=[O:62])[N:51]([CH:50]1[CH2:49][CH2:48][C:47](=[O:63])[NH:46][C:45]1=[O:44])[C:59]2=[O:60]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 157283,4-Dichlorobenzyl alcoholHCID 5363146Diisopropyl azodicarboxylateHCID 117780874-Hydroxy thalidomide

Product 1

HCID 25014965HCID 25014965, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of polymer-supported triphenylphosphine (1.46 g, ˜4.4 mmol) and 3,4-dichlorobenzyl alcohol (0.65 g, 3.6 mmol) was stirred in THF (10 mL) at 0° C. Keeping the reaction mixture at 0° C., a solution of diisopropylazodicarboxylate (0.87 mL, 4.4 mmol) in THF (2.1 mL) was added dropwise. 2-(2,6-Dioxo-piperidin-3-yl)-4-hydroxy-isoindole-1,3-dione (1.00 g, 3.60 mmol) was then added as a solid, the reaction mixture was stirred at 0° C. for 1 h and then at room temperature overnight. The solvent was evaporated under vacuum and the residue was chromatographed using a methanol-CH2Cl2 gradient, eluting the product at 95:5 CH2Cl2-methanol. This material was dissolved in ethyl acetate (150 mL) and water (100 mL) was added. The organic phase was then washed with 10% dilute aqueous sodium carbonate (2×50 mL) and water (3×50 mL). The solvent was removed under vacuum and the resulting solid was triturated with ether, filtered and dried to provide the title compound as a white solid (0.41 g, 26% yield); mp 245-247° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 3.50 (99.78%); 1H NMR (DMSO-d6) δ 2.02-2.07 (m, 1H), 2.45-2.62 (m, 2H), 2.82-2.96 (m, 1H), 5.12 (dd, J=12.6 Hz, J=5.4 Hz, 1H), 5.38 (s, 2H), 7.49-7.51 (m, 2H), 7.57 (d, J=8.5 Hz, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.81-7.88 (m, 2H), 11.12 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 48.8, 68.5, 115.9, 116.8, 120.1, 127.3, 129.0, 130.5, 130.8, 131.2, 133.3, 137.1, 137.5, 155.1, 165.3, 166.8, 169.9, 172.8; Anal. Calcd for C20H14N2O5Cl2+0.3 H2O: C, 54.76; H, 3.35; N, 6.39. Found: C, 54.48; H, 3.07; N, 6.29.

Workup

  1. customat 0° C.
  2. customat room temperature
  3. customovernight
  4. customThe solvent was evaporated under vacuum
  5. customthe residue was chromatographed
  6. washeluting the product at 95:5 CH2Cl2-methanol
  7. dissolutionThis material was dissolved in ethyl acetate (150 mL)
  8. additionwater (100 mL) was added
  9. washThe organic phase was then washed with 10% dilute aqueous sodium carbonate (2×50 mL) and water (3×50 mL)
  10. customThe solvent was removed under vacuum
  11. customthe resulting solid was triturated with ether
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-f8ffdecff155465cb5a34459e5437348
Source dataset
uspto-grants-2013_12
Patent number
US08614328B2

Reaction notes

Loading…