Hydrochloric Acid → HCID 69430634, compound

HRID 1295504Notes

Reaction equation

HRID 1295504 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH:16]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21](OS(C(F)(F)F)(=O)=O)[CH:20]=3)[CH:13]([CH2:14][CH2:15]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=[NH:46])(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH:16]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([NH2:46])[CH:20]=3)[CH:13]([CH2:14][CH2:15]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 634876Binap, (A+-)-HCID 86595512HCID 86595512, compound

Product 1

HCID 69430634HCID 69430634, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
80 °C

Procedure

8-[3-(Trifluoro-methanesulfonyloxy)-phenyl]-3-aza-bicyclo[3.2.1]octane-3-carboxylic acid benzyl ester (800 mg, theoretical amount 1.24 mmol) was azeotroped with THF (2×20 mL) then dissolved in anhydrous THF (10 mL) with benzophenone imine (0.260 mL, 1.55 mmol), cesium carbonate (606 mg, 1.86 mmol) and BINAP (racemic, 77 mg, 0.12 mmol). The reaction vessel was degassed (evac./N2 purge 3×) before charging with palladium (II) acetate (28 mg, 0.12 mmol). The reaction was warmed to 80° C. 18 h, at which point it was judged complete by APCI MS. To this was added fresh THF (10 mL) followed by 2N HCl (5 mL) and this solution was allowed to stir at room temperature 30 min. The reaction mixture was neutralized with saturated aqueous NaHCO3 solution. The product was extracted with EtOAc (3×30 mL), washed with saturated aqueous NaCl solution (1×30 mL), dried over Na2SO4 and concentrated to give the crude product. Flash chromatography provided the title compound as a thick yellow oil (236 mg, 57%). (TLC 30% EtOAc/hexanes Rf 0.15). 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 2H), 7.30 (m, 3H), 7.10 (m, 1H), 6.65 (m, 1H), 6.55 (m, 2H), 5.15 (s, 2H), 4.07 (dd, J=12.5, 2.5 Hz, 1H), 3.99 (dd, J=12.5, 2.5 Hz, 1H), 3.13 (d, J=12.5 Hz, 1H), 3.08 (d, J=12.5 Hz, 1H), 2.86 (s, 1H), 2.55 (brs, 1H), 2.48 (br s, 1H), 1.69 (m, 2H), 1.52 (m, 2H). APCI MS m/z 338.1 (M+1)+; 378.3 (M+CH3CN)+.

Workup

  1. customThe reaction vessel was degassed
  2. custom(evac./N2 purge 3×)
  3. custom18 h
  4. extractionThe product was extracted with EtOAc (3×30 mL)
  5. washwashed with saturated aqueous NaCl solution (1×30 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give the crude product

Sources & evidence

ORD record
ord-1986a1bbe37e4de4b35c4c01fe35cc0b
Source dataset
uspto-grants-2007_07
Patent number
US07241887B2

Reaction notes

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