Toluene → HCID 178514666, compound

HRID 1893031Notes

Reaction equation

HRID 1893031 reaction equation
COC1C=CC(C(C2C=CC(OC)=CC=2)[O:10][CH:11](C2C=CC=CC=2)[CH:12]2[CH2:16][CH:15]([OH:17])[CH2:14][N:13]2C(=O)CCCCC[N:24]2[C:32](=[O:33])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]2=[O:34])=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>ClCCl.CCCCCC>[OH:17][CH:15]1[CH2:14][NH:13][C@H:12]([CH2:11][OH:10])[CH2:16]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

7

Reactant 4

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 1281532-Cyanoethyl tetraisopropylphosphorodiamiditeHCID 1317282162-(6-{2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-isoindole-1,3-dione

Product 1

HCID 178514666HCID 178514666, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

Compound 44a (9.0 g, 13.57 mmol) was coevaporated with anhydrous toluene (50 mL) To the residue N,N-tetraisopropylammonium tetrazolide (0.766 g, 6.8 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 dichloromethane (20 mL) and 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (6.13 g, 6.7 mL, 20.35 mmol) was added. The reaction mixture was stirred at ambient temperature for overnight. The completion of the reaction was ascertained by TLC (Rf=0.7 in 1:1 ethyl acetate:hexane). The reaction mixture was diluted with dichloromethane (100 mL) and 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 45a as white solid (10.5 g, 89%).

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 dichloromethane (20 mL)
  4. washwashed with 5% NaHCO3 (100 mL) and brine (100 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified over silica gel (50:49:1, EtOAc:Hexane:triethlyamine)

Sources & evidence

ORD record
ord-72dc91cd189f45948418963d1d6fac07
Source dataset
uspto-grants-2013_08
Patent number
US08507661B2

Reaction notes

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