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Tetrahydrofuran → tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

HRID 1994510
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1994510
C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([C:50]1[CH:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[C:52]([C:60]([F:63])([F:62])[F:61])[CH:51]=1)O)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1C1C=C(C(C)C)C=CC=1OC)([CH3:21])([CH3:20])[CH3:19].C1C=CC(P([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81]C=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=N[C:87](OCC)=O.[CH2:97]1[CH2:101][O:100][CH2:99][CH2:98]1>CCOC(C)=O>[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([N:15]=[N+:16]=[N-:17])[C:50]1[CH:51]=[C:52]([C:60]([F:62])([F:61])[F:63])[CH:53]=[C:54]([C:56]([F:57])([F:58])[F:59])[CH:55]=1)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=1[C:97]1[CH:98]=[C:83]([CH:82]([CH3:81])[CH3:87])[CH:84]=[CH:79][C:101]=1[O:100][CH3:99])([CH3:19])([CH3:20])[CH3:21]
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Komponenten

7

Edukt 5

HCID 8028Tetrahydrofuran2×HCID 11776Triphenylphosphine2×HCID 199401P,P-Diphenylphosphinic azide2×HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 87121496Tert-butyl{(1s,2s)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Produkt 1

HCID 86603415tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A dry flask was charged with THF (1 mL) diethyl azodicarboxylate (DEAD) (11 μL, 0.0698 mmol) and diphenylphosphoryl azide (DPPA) (15 μL, 0.0698 mmol). tert-butyl{(1S,2S)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (20.7 mg, 0.0698 mmol) was added by cannula in THF (1 mL). Next Ph3P (18.3 mg, 0.0698 mmol) was added. The reaction was stirred at room temperature for 30 min, and then additional DEAD (11 μL, 0.0698 mmol), DPPA (15 μL, 0.0698 mmol), and Ph3P (18.3 mg, 0.0698 mmol) were added. After an additional 30 min, the reaction was diluted with EtOAc (40 mL) and washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 15% EtOAc/hexanes afforded tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.60 (25% EtOAc/hexanes). LCMS=619.3 (M+1−BOC)+.

Aufarbeitung

  1. waitAfter an additional 30 min
  2. washwashed with water and brine (15 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 15% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-55052fbf903543fca87f9601c5f2451b
Quelldatensatz
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07652049B2

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