Triethylamine → [(R)-3-((S)-2-benzyloxycarbonylamino-3-methyl-butyrylamino)-2-hydroxy-propyl]-cyclohexylmethyl-phosphinic acid benzyl ester

HRID 72149

Reaktionsgleichung

Reaktionsgleichung von HRID 72149
[C:1]([NH:11][C@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].OC1C2N=NNC=2C=CC=1.N=C=N.C(N(CC)CC)C.Cl.[CH2:40]([O:47][P:48]([CH2:57][C@H:58]([OH:61])[CH2:59][NH2:60])([CH2:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1)=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[CH2:40]([O:47][P:48]([CH2:57][C@H:58]([OH:61])[CH2:59][NH:60][C:16](=[O:18])[C@@H:12]([NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH:13]([CH3:14])[CH3:15])([CH2:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1)=[O:49])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 160435CarbodiimideHCID 726987N-Carbobenzoxy-L-valineHCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochlorideHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 68620942[(R)-3-((S)-2-benzyloxycarbonylamino-3-methyl-butyrylamino)-2-hydroxy-propyl]-cyclohexylmethyl-phosphinic acid benzyl esterAusbeute 26,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of N-Cbz-L-valine (1.0 g, 3.98 mmol) dissolved in CH2Cl2 (80 mL) under nitrogen was added hydroxybenzotriazole (0.538 g, 3.98 mmol) and PS-Carbodiimide (2.25 g, 5.17 mmol). After stirring for 10 min, triethylamine (0.665 mL, 4.78 mmol) and ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride (1.44 g, 3.98 mmol) were added. The reaction was stirred for 2 h, then filtered and concentrated in vacuo. The residue was purified by flash chromatography with methanol/dichloromethane on a 35 g RediSep disposable column to give [(R)-3-((S)-2-benzyloxycarbonylamino-3-methyl-butyrylamino)-2-hydroxy-propyl]-cyclohexylmethyl-phosphinic acid benzyl ester (0.60 g, 1.07 mmol) as a white foam. NMR and MS spectra were substantially similar to the product obtained via Method A set forth above.

Aufarbeitung

  1. stirringThe reaction was stirred for 2 h
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography with methanol/dichloromethane on a 35 g RediSep disposable column

Quellen und Nachweise

ORD-Eintrag
ord-3566b976c00948f68d243c612bfd079f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828974B2

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