Triethylamine → 2-(t-Butyloxycarbonylamino)-4-(N-(Cbz-isoleucyl)amino)-1,5-diphenyl-3-hydroxypentane

HRID 1379409

Reaktionsgleichung

Reaktionsgleichung von HRID 1379409
[NH2:1][CH:2]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:3]([OH:20])[CH:4]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[N+](C1C=CC([O:37][C:38](=O)[C@H:39]([C@H:51]([CH2:53][CH3:54])[CH3:52])[NH:40][C:41]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:42])=CC=1)([O-])=O.C(N(CC)CC)C>C1COCC1.[OH-].[Na+].C(Cl)(Cl)Cl.CO>[C:16]([O:15][C:13]([NH:12][CH:4]([CH:3]([OH:20])[CH:2]([NH:1][C:38](=[O:37])[C@H:39]([C@H:51]([CH2:53][CH3:54])[CH3:52])[NH:40][C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Komponenten

8

Edukt 3

HCID 8471TriethylamineHCID 2063382N-[(Phenylmethoxy)carbonyl]-L-isoleucine 4-nitrophenyl esterHCID 147043774-Amino-2-(t-butyloxycarbonylamino)-1,5-diphenyl-3-hydroxypentane

Produkt 1

HCID 228456432-(t-Butyloxycarbonylamino)-4-(N-(Cbz-isoleucyl)amino)-1,5-diphenyl-3-hydroxypentaneAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittel2×HCID 6212ChloroformLösungsmittel4×HCID 8028TetrahydrofuranLösungsmittel2×HCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

The resultant compound of Example 11 (125 mg, 0.34 mmol), N-benzyloxycarbonyl-isoleucine p-nitrophenyl ester (196 mg, 0.51 mmol) and triethylamine (94 μL, 0.67 mmol) were combined with 1.0 mL of dry THF and stirred together at ambient temperature overnight. The reaction mixture was then heated at reflux temperature for 3 h. The cooled reaction mixture was then diluted with 5 mL of THF and 5 mL of 3M aqueous sodium hydroxide solution was added. The mixture was stirred at ambient temperature for approximately 0.5 h. and was then diluted with chloroform. The chloroform solution was washed with 3×25 mL of 0.5M aqueous sodium hydroxide solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue (227 mg) was taken up in approximately 5 mL of chloroform and applied to a 1.0×45 cm column of 40 mesh silica gel. The column was eluted @ 5-10 p.s.i. sequentially with 100 mL of chloroform, 100 mL of 0.5% methanol in chloroform and 100 mL of 1% methanol in chloroform to give 169 mg (81% yield) of the title compound; FAB MS M/Z: 618 (M+H)+. The 300 MHz 1H NMR spectrum was consistent with the assigned structure.

Aufarbeitung

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux temperature for 3 h
  3. customThe cooled reaction mixture
  4. additionwas added
  5. stirringThe mixture was stirred at ambient temperature for approximately 0.5 h.
  6. washThe chloroform solution was washed with 3×25 mL of 0.5M aqueous sodium hydroxide solution and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. washThe column was eluted @ 5-10 p.s.i

Quellen und Nachweise

ORD-Eintrag
ord-a6c6bd8b2bd44cc0a4b5939114f93be8
Quelldatensatz
uspto-grants-1997_09
Patentnummer
US05670675

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