Toluene → HCID 66863531, compound

HRID 751134Notes

Reaction equation

HRID 751134 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([Cl:32])[C:25]=1[CH3:33])[CH3:22])=O)(C)(C)C.C1(C)C=CC=CC=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Si:14]([O:13][C@H:10]1[CH2:11][CH2:12][NH:8][C@@H:9]1[C@@H:21]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([Cl:32])[C:25]=1[CH3:33])[CH3:22])([C:17]([CH3:19])([CH3:20])[CH3:18])([CH3:16])[CH3:15]

Participants

5

Reactant 2

HCID 1140Toluene2×HCID 16732285(2R,3S)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-1-(3-chloro-4-cyano-2-methyl-phenylamino)ethyl]pyrrolidine

Product 1

HCID 66863531HCID 66863531, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Intermediate 61H (825 mg, 1.67 mmol) was dried azeotropically with toluene (2×). The residue was taken up in 15% TFA in CH2Cl2 (10 mL) and stirred at rt for 5 h. Toluene (10 mL) was added and solvent was removed under vacuum. The product was purified by reverse phase HPLC (Phenoenex Luna 30×100 mm S5 C18, 10 min. grad, 25 mL/min, 20-100% B solvent, A=10% MeOH/water+0.1% TFA, B=90% MeOH/Water+0.1% TFA, 4 injections). Solvent was reduced to ˜10% volume and the product was then extracted into EtOAc, washed with sat. aqueous NaHCO3, dried over MgSO4 and filtered. Solvents were removed to provide the title compound (371 mg): MS (ES) m/z 394.53 [M+H]+

Workup

  1. customsolvent was removed under vacuum
  2. customThe product was purified by reverse phase HPLC (Phenoenex Luna 30×100 mm S5 C18, 10 min.
  3. extractionthe product was then extracted into EtOAc
  4. washwashed with sat. aqueous NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customSolvents were removed

Sources & evidence

ORD record
ord-7d57bd5f340c4eb88090cc7d1eb7a871
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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