Toluene → HCID 178420607, compound

HRID 1893048Notes

Reaction equation

HRID 1893048 reaction equation
COC1C=CC(C(C2C=CC(OC)=CC=2)OC(C2C=CC=CC=2)[CH:12]2[CH:16](O)[CH2:15][N:14](C(=O)CCCCC[N:24]3[C:32](=[O:33])[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:25]3=[O:34])[CH2:13]2)=CC=1.C1(C)C=CC=CC=1.C(CC[O:61][P:62]([N:70](C(C)C)C(C)C)N(C(C)C)C(C)C)#N.C(OCC)(=[O:79])C>CCCCCC>[NH:14]1[CH2:15][CH2:16][CH2:12][CH2:13]1.[P:62]([NH2:70])([O-:61])[O:79][N:24]1[C:32](=[O:33])[C:31]2=[CH:30][CH:29]=[CH:28][CH:27]=[C:26]2[C:25]1=[O:34]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 1281532-Cyanoethyl tetraisopropylphosphorodiamiditeHCID 1317282252-(6-{3-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-isoindole-1,3-dione

Product 1

HCID 178420607HCID 178420607, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Compound 77 (1.5 g, 2.26 mmol) was coevaporated with anhydrous toluene (25 mL) To the residue N,N-tetraisopropylammonium tetrazolide (0.127 g, 1.13 mmol) was added and the mixture was dried over P2O5 in a vacuum oven for overnight at 40° C. The reaction mixture was dissolved in acetonitrile/dichloroethane (10 mL) and 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (1.362 g, 1.49 mL, 4.52 mmol) was added. The reaction mixture was stirred at ambient temperature for overnight. The completion of the reaction was ascertained by TLC (Rf=0.4 in 1:1 ethyl acetate:hexane). The reaction mixture was concentrated undervacuum and the residue was dissolved in ethyl acetate (100 mL) The organic layer was washed with 5% NaHCO3 (100 mL) and brine (100 mL) The organic layer was dried over anhydrous Na2SO4 filtered and concentrated under reduced pressure. The residue was purified over silica gel (50:49:1, EtOAc:Hexane:triethlyamine) to afford compound 78 as white solid (1.66 g, 85%).

Workup

  1. additionwas added
  2. dry with materialthe mixture was dried over P2O5 in a vacuum oven for overnight at 40° C
  3. dissolutionThe reaction mixture was dissolved in acetonitrile/dichloroethane (10 mL)
  4. concentrationThe reaction mixture was concentrated undervacuum
  5. dissolutionthe residue was dissolved in ethyl acetate (100 mL) The organic layer
  6. washwas washed with 5% NaHCO3 (100 mL) and brine (100 mL) The organic layer
  7. dry with materialwas dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified over silica gel (50:49:1, EtOAc:Hexane:triethlyamine)

Sources & evidence

ORD record
ord-7fd5fcad88b64adeb4b194e6bfd2b832
Source dataset
uspto-grants-2013_08
Patent number
US08507661B2

Reaction notes

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