Trifluoroacetic acid → 4-Benzyl-1-[2(R)-tert-butoxycarbonylamino-3-triphenylmethylthiopropyl]-2(S)-(2-methoxyethyl)piperazine

HRID 1598457Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1598457
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[C@@H:10]([CH2:21][CH2:22][O:23][CH3:24])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:46]([O:50][C:51]([NH:53][C@@H:54]([CH2:57][S:58][C:59]([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)C=O)=[O:52])([CH3:49])([CH3:48])[CH3:47]>C(Cl)Cl.ClC(Cl)C>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C@@H:54]([NH:53][C:51]([O:50][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:52])[CH2:57][S:58][C:59]([C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=2)([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=2)[C@@H:10]([CH2:21][CH2:22][O:23][CH3:24])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 10388929N-Boc-S-trityl-(L)-cysteinalHCID 154060464-Benzyl-1-tert-butoxycarbonyl-2(S)-(2-methoxyethyl)piperazine

Produkt 1

HCID 228841624-Benzyl-1-[2(R)-tert-butoxycarbonylamino-3-triphenylmethylthiopropyl]-2(S)-(2-methoxyethyl)piperazine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 63651,1-DichloroethaneLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

4-Benzyl-1-tert-butoxycarbonyl-2(S)-(2-methoxyethyl)piperazine from Example 7, step C (1.17 g, 3.50 mmol) was dissolved in methylene chloride (20 mL). To this solution was added trifluoroacetic acid (10 mL) and the reaction stirred at 20° C. for 1 h. The volatiles were removed in vacuo and the residue taken up in dichloroethane (40 mL). Triethylamine was added to attain pH 7. To this solution was added crushed molecular seives (1 g), sodium triacetoxyborohydride (1.2 g, 5.3 mmol) and the reaction cooled to -15° C. with ice-methanol. A solution of 2(R)-tert-butoxycarbonylamino-3-triphenylmethylthiopropanal (1.72 g, 3.85 mmol) in dichloroethane (15 mL) was added slowly dropwise. The reaction was stirred at 20° C. overnight then quenched with saturated sodium bicarbonate. The organic phase was washed with saturated sodium chloride solution, and dried over magnesium sulfate. The crude product (2.52 g) was chromatographed on silica gel with 30% ethyl acetate in hexane using medium pressure liquid chromatography (MPLC). The title compound (Rf 0.21) was isolated as a gum (0.906 g). NMR (CHCl3, 300 MHz) δ 7.2-7.4 (20H, m), 4.70 (1H, d, J=8 Hz), 3.63 (1H, br s), 3.50 (1H, d, J=13 Hz), 3.36 (1H, d, J=13 Hz), 3.2-3.35 (5H, m), 2.75 (1H, m), 2.0-2.6 (10H, m), 1.75 (2H, m), 1.42 (9H, s). A diastereomeric minor product (Rf 0.14) was also isolated (0.065 g).

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. additionTriethylamine was added
  3. additionTo this solution was added
  4. stirringThe reaction was stirred at 20° C. overnight
  5. customthen quenched with saturated sodium bicarbonate
  6. washThe organic phase was washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. customThe crude product (2.52 g) was chromatographed on silica gel with 30% ethyl acetate in hexane using medium pressure liquid chromatography (MPLC)

Quellen und Nachweise

ORD-Eintrag
ord-d28522d89a6d4bf19e0cb866b4f518a6
Quelldatensatz
uspto-grants-1998_04
Patentnummer
US05736539

Notizen zur Reaktion

Wird geladen…