Triethylamine → HCID 86665793, Verbindung

HRID 590747Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 590747
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:21](O)=[O:22])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[N:48]([C@:51]1([C:68]([O:70][CH2:71][C:72](=[O:79])[C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)=[O:69])[C@@H:55]([CH2:56][CH2:57][CH2:58][B:59]2[O:63][C:62]([CH3:65])([CH3:64])[C:61]([CH3:67])([CH3:66])[O:60]2)[CH2:54][NH:53][CH2:52]1)=[N+:49]=[N-:50].CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[N:48]([C@:51]1([C:68]([O:70][CH2:71][C:72](=[O:79])[C:73]2[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=2)=[O:69])[C@@H:55]([CH2:56][CH2:57][CH2:58][B:59]2[O:60][C:61]([CH3:67])([CH3:66])[C:62]([CH3:65])([CH3:64])[O:63]2)[CH2:54][N:53]([C:21](=[O:22])[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][CH:12]=2)[NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:52]1)=[N+:49]=[N-:50]

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7021025N-((1,1-Dimethylethoxy)carbonyl)-4-(trifluoromethyl)-L-phenylalanineHCID 131734493HCID 131734493, Verbindung

Produkt 1

HCID 86665793HCID 86665793, VerbindungAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

A mixture of N-(tert-butoxycarbonyl)-4-(trifluoromethyl)phenylalanine (268 mg, 0.804 mmol), 1-hydroxybenzotriazole hydrate (123 mg, 0.804 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (154 mg, 0.804 mmol) in dry methylene chloride (10 mL) and DMF (3 mL) was stirred at room temperature. After 1 h, a second solution of racemic 2-oxo-2-phenylethyl (3R,4S)-3-azido-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]pyrrolidine-3-carboxylate hydrochloride (350 mg, 0.73 mmol) in methylene chloride (3.5 mL) was added, followed immediately by Et3N (204 uL, 1.46 mmol), and the resulting homogeneous mixture was stirred at room temperature for 3.5 h. Once complete, the mixture was diluted with dichloromethane (8 mL), washed successively with water (2×20 mL), saturated aqueous NaHCO3 (2×20 mL) and saturated aqueous sodium chloride, dried over Na2SO4 and concentrated. Purification by silica gel chromatography (90 g column, 15-35% ethyl acetate in hexanes) gave 2-oxo-2-phenylethyl (3R,4S)-3-azido-1-[N-(tert-butoxycarbonyl)-4-(trifluoromethyl)phenylalanyl]-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]pyrrolidine-3-carboxylate (233 mg, ˜60% purity) as a white foam which was used without further purification. LC-MS ESI+ MS found for C37H47BF3N5O8 m/z 758.3 (M+H), 780.3 (M+Na); ESI− MS m/z 756.5 (M−H).

Aufarbeitung

  1. stirringthe resulting homogeneous mixture was stirred at room temperature for 3.5 h
  2. washwashed successively with water (2×20 mL), saturated aqueous NaHCO3 (2×20 mL) and saturated aqueous sodium chloride
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (90 g column, 15-35% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a552bee288ff422aa99c07d1ee9c82ac
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233985B2

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