Trifluoroacetate → HCID 178461409, compound

HRID 1694396Notes

Reaction equation

HRID 1694396 reaction equation
[Cl:1][C:2]1[CH:14]=[C:13]([C:15]2[CH2:18][CH:17]([C:19]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:20])[CH:16]=2)[CH:12]=[CH:11][C:3]=1[CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[CH3:10].FC(F)(F)C([O-])=O>C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[ClH:1].[Cl:1][C:2]1[CH:14]=[C:13]([C@H:15]2[CH2:18][C@H:17]([C:19]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:20])[CH2:16]2)[CH:12]=[CH:11][C:3]=1[CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[CH3:10]

Participants

5

Reactant 2

HCID 84468TrifluoroacetateHCID 86619853HCID 86619853, compound

Product 1

HCID 178461409HCID 178461409, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 702EthanolSolvent

Procedure

To a solution of Intermediate 6, (2R)-1-{2-chloro-4-[3-(pyrrolidin-1-ylcarbonyl)cyclobut-1-en-1-yl]benzyl}-2-methylpyrrolidine, trifluoroacetate (1.06 mmol) in 5 mL of ethanol was added chlorotris(triphenylphosphine)rhodium(I) (100 mg, 0.106 mmol). The mixture was hydrogenated (40 psi H2, at 50° C.) for 3 h. The reaction was monitored by LCMS. The mixture was evaporated to dryness, then 5 ml of 1 N HCl was added to the residue and the solution was extracted with ethyl acetate (2×5 ml), the organic layers were discarded. 10N NaOH (1 mL) was added to the water layer and the water solution was extracted with ethyl acetate (3×5 mL). The organic layers were dried and evaporated in vacuo. The residue was purified by chromatography (SiO2 63/100 μm, 10 g, CHCl3/hexane 80:20→100:0, CHCl3/MeOH 100:0→90:10). The product containing fractions were collected and concentrated under reduced pressure. The residue was dissolved in 2 ml of ether and 0.1 mL of 4N HCl/dioxane was added under stirring. The solvent was evaporated; the residue was dried in vacuum to afford the HCl salt of the title compound (80 mg, 20%) as a dark yellow amorphous solid. LCMS data: 361 and 363 (M+H)+ (calculated for C21H29ClN2O 360.93). 1H NMR data (CD3OD): δ 7.63 (d, 1H, J=7.5 Hz), 7.50 (s, 1H), 7.39 (d, 1H, J=7.5 Hz), 4.75 (d, 1H, J=13.3 Hz), 4.31 (d, 1H, J=13.3 Hz), 3.63-3.77 (m, 2H), 3.34-3.52 (m, 7H), 2.64-2.75 (m, 2H), 2.33-2.49 (m, 3H), 1.72-2.20 (m, 7H), 1.51 (d, 3H, J=6.3 Hz).

Workup

  1. custom(40 psi H2, at 50° C.)
  2. customfor 3 h
  3. customThe mixture was evaporated to dryness
  4. addition5 ml of 1 N HCl was added to the residue
  5. extractionthe solution was extracted with ethyl acetate (2×5 ml)
  6. addition10N NaOH (1 mL) was added to the water layer
  7. extractionthe water solution was extracted with ethyl acetate (3×5 mL)
  8. customThe organic layers were dried
  9. customevaporated in vacuo
  10. customThe residue was purified by chromatography (SiO2 63/100 μm, 10 g, CHCl3/hexane 80:20→100:0, CHCl3/MeOH 100:0→90:10)
  11. additionThe product containing fractions
  12. customwere collected
  13. concentrationconcentrated under reduced pressure
  14. dissolutionThe residue was dissolved in 2 ml of ether
  15. addition0.1 mL of 4N HCl/dioxane was added
  16. customThe solvent was evaporated
  17. customthe residue was dried in vacuum

Sources & evidence

ORD record
ord-18f3aef537174b7d8dc98634e64a9d33
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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