Triethylamine → Tert-butyl 1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate

HRID 1804520Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1804520
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]([OH:18])=O)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O[N:20]=[C:21]([C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]2)=[CH:25][C:24]=1[C:41]([F:44])([F:43])[F:42])[NH2:22].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C>CN(C)C=O.ClCCl>[C:1]1([C:7]2[C:11]([C:12]([F:13])([F:14])[F:15])=[C:10]([C:16]3[O:18][N:22]=[C:21]([C:23]4[CH:40]=[CH:39][C:26]([CH2:27][N:28]5[CH2:29][CH:30]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:31]5)=[CH:25][C:24]=4[C:41]([F:44])([F:42])[F:43])[N:20]=3)[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 583740941236188-80-9HCID 86659948tert-butyl 1-(4-(N'-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate

Produkt 1

HCID 86659949Tert-butyl 1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylateAusbeute 16,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylic acid (0.030 g, 0.104 mmol), tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.039 g, 0.104 mmol), BOP-Cl (0.035 g, 0.136 mmol), and triethylamine (0.044 mL, 0.313 mmol) in N,N-dimethylformamide (1 mL) was shaken on platform shaker at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by flash silica gel chromatography using a mixture of 20% mixture of ethyl acetate in hexane to give tert-butyl 1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.010 g, 0.017 mmol, 16% yield) as a white solid. The compound had an HPLC ret. time=3.16 min.−Column. CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=595.2.

Aufarbeitung

  1. washwashed with a saturated aqueous solution of sodium bicarbonate
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash silica gel chromatography
  5. additiona mixture of 20% mixture of ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-3e889b5424fd4bca955c59ef4ccd3227
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354398B2

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