Trifluoroacetic acid → 2-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-{[(2R)-2-pyrrolidinylmethyl]oxy}benzamide

HRID 1623785Notes

Reaction equation

HRID 1623785 reaction equation
FC(F)(F)C(O)=O.[C:8]1([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@H:24]3[CH2:28][CH2:27][CH2:26][N:25]3C(OC(C)(C)C)=O)=[CH:18][C:17]=2[C:36]([NH:38][C:39]2[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=2)=[O:37])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C([O-])(O)=O.[Na+]>ClCCl>[C:8]1([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@H:24]3[CH2:28][CH2:27][CH2:26][NH:25]3)=[CH:18][C:17]=2[C:36]([NH:38][C:39]2[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=2)=[O:37])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 866682001,1-Dimethylethyl (2R)-2-[({4-[(phenylmethyl)oxy]-3-[(3-pyridinylamino)carbonyl]phenyl}oxy)methyl]-1-pyrrolidinecarboxylate

Product 1

HCID 699366462-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-{[(2R)-2-pyrrolidinylmethyl]oxy}benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Trifluoroacetic acid (1.5 ml, 19.47 mmol) was added dropwise to an ice-cooled solution of 1,1-dimethylethyl (2R)-2-[({4-[(phenylmethyl)oxy]-3-[(3-pyridinylamino)carbonyl]phenyl}oxy)methyl]-1-pyrrolidinecarboxylate (may be prepared as described in Description 73; 500 mg, 0.99 mmol) in dichloromethane (15 ml). After stirring at 25° C. for 2 h, the pH of the solution was adjusted to 7-8 by adding aqueous NaHCO3 solution. The mixture was extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over Na2SO4, and concentrated to obtain a crude product. Half of the crude product was purified by pre-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm; A: 0.04% NH3.H2O/water, B: CH3CN; 0-7 min, 35%-50%; 7-14 min, 95%; RT=6.5 min) to yield the title compound as a light yellow solid. 70 mg.

Workup

  1. extractionThe mixture was extracted with dichloromethane
  2. washThe dichloromethane layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto obtain a crude product
  6. customHalf of the crude product was purified by pre-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm
  7. custom0-7 min, 35%-50%
  8. custom7-14 min, 95%

Sources & evidence

ORD record
ord-4963f6137c2a4ac4b865ea375ebb1e15
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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