Trifluoroacetic acid → HCID 44302642, compound

HRID 1377762Notes

Reaction equation

HRID 1377762 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@H:15]3[C@H:19]([C:20]([O:22][CH3:23])=[O:21])[CH2:18][N:17]([C:24]([O:26]C(C)(C)C)=O)[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C[Si]([N:42]=C=O)(C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[NH2:42][C:24]([N:17]1[CH2:18][C@@H:19]([C:20]([O:22][CH3:23])=[O:21])[C@H:15]([C:9]2[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH:8]=2)[CH2:16]1)=[O:26]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 70696Trimethylsilyl isocyanateHCID 11742832HCID 11742832, compound

Product 1

HCID 44302642HCID 44302642, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-3-(3-cyclopentoxy-4-methoxyphenyl)-1-(1,1-dimethylethoxycarbonyl)-4-(methoxycarbonyl)pyrrolidine (419 mg, 1.0 mmol) in 2 mL of CH2Cl2 at 0° C. was added 2.3 mL of trifluoroacetic acid. The solution was stirred for 12 hr at room temperature, and concentrated to an oil. The oil was dissolved in 2 mL of CH2Cl2 and 4-dimethylaminopyridine 366 mg, 3.0 mmol) was added. To this solution at 0° C. was added trimethylsilylisocyanate (1.15 g, 10.0 mmol). The bath was removed and the resulting mixture was allowed to stir for 60 hr. After dilution with CH2Cl2, the reaction mixture was washed with 1M H3PO4 and brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Silica gel chromatography (9:1, CH2Cl2 :methanol) provided a foam. Crystallization with diisopropyl ether afforded trans-1-aminocarbonyl-3-(3-cyclopentoxy-4-methoxyphenyl)-4-(methoxycarbonyl)pyrrolidine as a white solid (243 mg, 67%), m.p. 127°-129° C. Anal. Calcd for C19H26N2O5 : C, 62.97; H, 7.23; N, 7.73. Found: C, 63.07; H, 7.20; N, 7.76.

Workup

  1. concentrationconcentrated to an oil
  2. dissolutionThe oil was dissolved in 2 mL of CH2Cl2
  3. customThe bath was removed
  4. stirringto stir for 60 hr
  5. washAfter dilution with CH2Cl2, the reaction mixture was washed with 1M H3PO4 and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customSilica gel chromatography (9:1, CH2Cl2 :methanol) provided a foam
  10. customCrystallization with diisopropyl ether

Sources & evidence

ORD record
ord-723cef79f0e240459a5fc0a1ab56e099
Source dataset
uspto-grants-1997_09
Patent number
US05665754

Reaction notes

Loading…