Trifluoroacetate → HCID 178484581, compound

HRID 1694392Notes

Reaction equation

HRID 1694392 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][C:3]=1[C:15]1[CH2:18][CH:17]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH:16]=1.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[C:7]([Cl:8])=[C:6]([CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][C:3]=1[C@H:15]1[CH2:18][C@H:17]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:16]1

Participants

5

Reactant 2

HCID 84468TrifluoroacetateHCID 87336467HCID 87336467, compound

Product 1

HCID 178484581HCID 178484581, compoundYield 28%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of intermediate 2, 3-[2,3-dichloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N,N-dimethylcyclobut-2-ene-1-carboxamide, trifluoroacetate (0.673 mmol) in 5 mL of ethanol was added chlorotris(triphenylphosphine)rhodium(I) (63 mg, 0.0673 mmol). The mixture was hydrogenated (40 psi H2, 50%) 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 vacuum. The residue was purified by chromatography (SiO2 63/100 μm, 10 g, CHCl3/hexane 80:20→100:0, CHCl3/MeOH 100:0→90:10). Fractions containing the product were evaporated. The residue was dissolved in 2 ml of ether and 0.1 mL of 4N HCl/dioxane was added under stirring. The mixture was evaporated; the residue was dried in vacuum to afford the title compound (74 mg, 28%) as a white solid. LCMS data: 355, 356, and 357 (M+H)+ (calculated for C18H24Cl2N2O 355.31). 1H NMR data (CD3OD): δ 7.69 (d, 1H, J=8.1 Hz), 7.58 (d, 1H, J=8.1 Hz), 4.62 (s, 2H), 3.88-3.98 (m, 1H), 3.54-3.63 (m, 2H), 3.35-3.45 (m, 1H), 3.25-3.34 (m, 2H+MeOH), 2.99 (s, 6H), 2.71-2.79 (m, 2H), 2.42-2.52 (m, 2H), 2.16-2.27 (m, 2H), 1.98-2.12 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-963470e71cb9424c9b9ceb8c892a71cc
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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