Hydrochloric Acid → HCID 178499535, compound

HRID 2200812Notes

Reaction equation

HRID 2200812 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](=[NH:5])[NH2:4].[CH3:8][O:9][C:10](=[O:19])[CH2:11][C:12](=O)[CH2:13][C:14](OC)=[O:15].Cl.CCCCCC>C[O-].[Na+].CO.CC(O)C.CCOC(C)=O>[OH:15][C:14]1[N:4]=[C:3]([C:2]([F:7])([F:6])[F:1])[N:5]=[C:12]([CH2:11][C:10]([O:9][CH3:8])=[O:19])[CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8058HexaneHCID 74591Dimethyl 3-oxoglutarateHCID 2776882Trifluoroacetamidine

Product 1

HCID 178499535HCID 178499535, compoundYield 69.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 10942334Sodium MethoxideSolventHCID 22055037Isopropanol ethyl acetateSolvent

Conditions

Temperature
50 °C

Procedure

2,2,2-Trifluoroethanimidamide (6.7 g, 50. mmol, Oakwood) was dissolved in 0.5 M sodium methoxide in methanol (120 mL, 60. mmol) and 3-oxopentanedioic acid dimethyl ester (8.4 mL, 55 mmol, Aldrich Co.) was added. The reaction solution was stirred 50° C. for 18 h. LCMS showed it to be mostly done to give the product, M+H 237. The solvent was rotovapped. 1 N HCl was added (50 mL) (pH5), followed 4M HCl (10 mL). The mixture was then extracted with ethyl acetate. The organic solution was washed with brine, dried over sodium sulfate, filtered and concentrated to 12 g of a yellow semisolid. The product was isolated by automatic silica gel chromatography on a 120 g silica gel column, using solvent A=hexane; solvent B=3% iPrOH/EtOAc; flow 60 mL/min; A, 3 min; gradient to 30% B in 40 min, then 30% B for 20 min; detector set at 256 nm; collected 47 mL fractions. The product eluted at 10-25 min. HPLC showed UVmax at 222 and 254 nm (dropping off to 320 nm). The solvent was removed to give 9 g of product. The product was purified by automatic silica gel chromatography on a 120 g silica gel column, using solvent A=hexane; solvent B=iPrOH; flow 60 mL/min; A, 3 min; gradient to 20% B in 25 min, then 20% B for 10 min; detector set at 264 nm; collected 47 mL fractions. The product eluted at 22-27 min. The solvent was removed by rotary evaporation to give the desired product as light yellow viscous oil, 5.2 g, which slowly began to crystallize. NMR (400 MHz, DMSO-D6) δ 6.95 (s, 1H); 3.87 (s, 2H, ArCH2); 3.63 (s, 3H).

Workup

  1. customto give the product, M+H 237
  2. extractionThe mixture was then extracted with ethyl acetate
  3. washThe organic solution was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to 12 g of a yellow semisolid
  7. customThe product was isolated by automatic silica gel chromatography on a 120 g silica gel column
  8. custom3 min
  9. waitgradient to 30% B in 40 min
  10. wait30% B for 20 min
  11. customcollected 47 mL fractions
  12. washThe product eluted at 10-25 min
  13. customThe solvent was removed

Sources & evidence

ORD record
ord-1712255134e34c50bd195113a6ec68a1
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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