1,2-Dichloroethane → HCID 69938762, Verbindung

HRID 1058262Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1058262
C([N:18]1[CH2:25][CH2:24][CH2:23][C@H:19]1[C:20](O)=[O:21])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.[NH2:26][CH2:27][C:28]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=1[CH:35]1[CH2:38][CH2:37][N:36]1[C:39]([O:41][CH2:42][C:43]([Cl:46])([Cl:45])[Cl:44])=[O:40].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:34][C:32]1[CH:31]=[CH:30][C:29]([CH:35]2[CH2:38][CH2:37][N:36]2[C:39]([O:41][CH2:42][C:43]([Cl:45])([Cl:46])[Cl:44])=[O:40])=[C:28]([CH2:27][NH:26][C:20](=[O:21])[C@@H:19]2[CH2:23][CH2:24][CH2:25][NH:18]2)[CH:33]=1

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 688135Fmoc-Pro-OHHCID 186723262,2,2-Trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate

Produkt 1

HCID 69938762HCID 69938762, VerbindungAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

N-Fmoc-L-proline (0.249 g, 0.739 mmol) was added to a stirred mixture of 2,2,2-trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate (0.275 g, 0.739 mmol), EDC (0.213 g, 1.11 mmol) and HOAT (50 mg, 0.37 mmol) in DMF (2 mL). After 16 h the reaction mixture was partitioned between ethyl acetate and dilute HCl solution. The organic layer was washed with water and brine, dried (Na2SO4) and evaporated in vacuo to a foam. This material was dissolved in DMF (2 mL) and piperidine (0.5 mL) and stirred for 30 min. The solution was poured into water (50 mL) and the precipitated solids were removed by filtration, washing with water (5×10 mL, which was collected and set aside) and methanol. The methanol was evaporated in vacuo and the residue was purified by flash column chromatography on silica (eluting with ethyl acetate followed by chloroform/methanol/ammonium hydroxide, 90:9:1) to give 2,2,2-trichloroethyl 2-{4-chloro-2-[(L-prolylamino)methyl]phenyl}azetidine-1-carboxylate (66 mg) as a gum. The milky aqueous washings were extracted into ethyl acetate (adding brine to dispel the emulsion) and the organic layer was washed with water and brine, dried (Na2SO4) and evaporated in vacuo to give more of the desired compound (0.206 g) as a gum: MS 468.5 (M+1) with an isotope distribution consistent with four chlorines.

Aufarbeitung

  1. customAfter 16 h the reaction mixture was partitioned between ethyl acetate and dilute HCl solution
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo to a foam
  5. dissolutionThis material was dissolved in DMF (2 mL)
  6. additionThe solution was poured into water (50 mL)
  7. customthe precipitated solids were removed by filtration
  8. washwashing with water (5×10 mL, which
  9. customwas collected
  10. customThe methanol was evaporated in vacuo
  11. customthe residue was purified by flash column chromatography on silica (eluting with ethyl acetate followed by chloroform/methanol/ammonium hydroxide, 90:9:1)

Quellen und Nachweise

ORD-Eintrag
ord-d4e8532977814f41aed7150ca66398b2
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06515011B2

Notizen zur Reaktion

Wird geladen…