Trifluoroacetic acid → 2,2-dimethyl-1-(2-phenoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-propan-1-one

HRID 600386Notes

Reaction equation

HRID 600386 reaction equation
[CH3:1][C:2]([CH3:30])([CH3:29])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:12]=2)[N:7](COCC[Si](C)(C)C)[CH:6]=1)=[O:4].FC(F)(F)C(O)=O.O.O.O.C([O-])(=O)C.[Na+]>ClCCl>[CH3:1][C:2]([CH3:30])([CH3:29])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:12]=2)[NH:7][CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23665404Sodium Acetate Trihydrate2×HCID 578310492,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one

Product 1

HCID 442003322,2-dimethyl-1-(2-phenoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-propan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of impure 2,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one, prepared according to general procedures as described in these Examples, (0.032 g, “0.075 mmol”) in 1 mL of dichloromethane and 1 mL of trifluoroacetic acid was stirred for 13 h, then concentrated to a yellow-green oil, which was partitioned between 5 mL of a sat. aq. NaHCO3 solution and 5 mL of dichloromethane. The aqueous layer was extracted with 5 mL of dichloromethane, and the combined organic layers were dried over MgSO4, filtered and concentrated to a pale yellow oil. The oil was dissolved in 1 mL of ethanol and treated with sodium acetate trihydrate (0.103 g, 0.756 mmol). The mixture was stirred for 2 h, then concentrated. The residue was partitioned between 5 mL of water and 5 mL of dichloromethane. The aqueous layer was extracted with 5 mL of dichloromethane, and the combined organic layers were dried over MgSO4, filtered and concentrated to a pale yellow oil. The oil was again dissolved in 1 mL of ethanol and treated with sodium acetate trihydrate (0.101 g, 0.745 mmol). The mixture was stirred for 4 h, then concentrated. The residue was partitioned between 5 mL of water and 5 mL of dichloromethane. The aqueous layer was extracted with 5 mL of dichloromethane, and the combined organic layers were dried over MgSO4, filtered and concentrated to an off-white solid. Column chromatography (0→33% EtOAc/hexanes) afforded 0.014 g (65% from impure; 40% 2-step) of 2,2-dimethyl-1-(2-phenoxy-5H-pyrrolo[2,3-b]pyrazin-7-yl)-propan-1-one as an off-white solid.

Workup

  1. concentrationconcentrated to a yellow-green oil, which
  2. customwas partitioned between 5 mL of a sat. aq. NaHCO3 solution and 5 mL of dichloromethane
  3. extractionThe aqueous layer was extracted with 5 mL of dichloromethane
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a pale yellow oil
  7. dissolutionThe oil was dissolved in 1 mL of ethanol
  8. concentrationconcentrated
  9. customThe residue was partitioned between 5 mL of water and 5 mL of dichloromethane
  10. extractionThe aqueous layer was extracted with 5 mL of dichloromethane
  11. dry with materialthe combined organic layers were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated to a pale yellow oil
  14. dissolutionThe oil was again dissolved in 1 mL of ethanol
  15. stirringThe mixture was stirred for 4 h
  16. concentrationconcentrated
  17. customThe residue was partitioned between 5 mL of water and 5 mL of dichloromethane
  18. extractionThe aqueous layer was extracted with 5 mL of dichloromethane
  19. dry with materialthe combined organic layers were dried over MgSO4
  20. filtrationfiltered
  21. concentrationconcentrated to an off-white solid

Sources & evidence

ORD record
ord-323fbe37de5a4eb582f02dbd45d38a90
Source dataset
uspto-grants-2011_03
Patent number
US07902197B2

Reaction notes

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