Trifluoroacetic acid → HCID 86709696, Verbindung

HRID 2285401

Reaktionsgleichung

Reaktionsgleichung von HRID 2285401
[Cl:1][C:2]([Cl:28])([Cl:27])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15]C(C)(C)C)=O)[N:8]1C(OC(C)(C)C)=O)=[O:6].FC(F)(F)C(O)=O.[C:36]([O:40][C:41]([NH:43][C@@H:44]([CH2:48][O:49][CH:50]([F:52])[F:51])C(O)=O)=[O:42])([CH3:39])([CH3:38])[CH3:37].F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(CC)C(C)C)(C)C>ClCCl.C(#N)C>[Cl:28][C:2]([Cl:1])([Cl:27])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:15])[C@@H:44]([NH:43][C:41]([O:40][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:42])[CH2:48][O:49][CH:50]([F:52])[F:51])[NH:8]1)=[O:6]

Komponenten

8

Edukt 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 86706063HCID 86706063, VerbindungHCID 86709693(S)-2-tert-Butoxycarbonylamino-3-difluoromethoxy-propionic acidHCID 178484293HCID 178484293, Verbindung

Produkt 1

HCID 86709696HCID 86709696, VerbindungAusbeute 28,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A cooled (0° C.) solution of (S)-tetrahydro-pyridazine-1,2,3-tricarboxylic acid 1,2-di-tert-butyl ester 3-(2,2,2-trichloro-ethyl)ester (923 mg, 2.0 mmol) in dichloromethane (3 mL) was treated with trifluoroacetic acid (3 mL). After stirring at room temperature for 1.5 h, the volatiles were removed in vacuo and residual trifluoroacetic acid was azeotroped off with toluene. The residue was combined with (S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionic acid (260 mg, 1.02 mmol) and dissolved in anhydrous acetonitrile (10 mL). The cooled (0° C.) mixture was subsequently treated with 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (543 mg, 1.43 mmol) and N,N-diisopropylethylamine (0.71 mL, 4.08 mmol). After stirring at room temperature for 3 days, the volatiles were removed in vacuo and the residue was partitioned between ethyl acetate and water. The organics were separated, dried over anhydrous sodium sulfate, filtered and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography eluting with a stepwise gradient of iso-hexanes/ethyl acetate 1:0 to 7:3 to provide the title compound (143 mg, 28%) as a pale Greene gum and as a complex mixture of rotamers. LCMS (m/z) 498.0, 500.0 [M+H], Tr=2.91 min.

Aufarbeitung

  1. customthe volatiles were removed in vacuo and residual trifluoroacetic acid
  2. customwas azeotroped off with toluene
  3. temperatureThe cooled (0° C.) mixture
  4. stirringAfter stirring at room temperature for 3 days
  5. customthe volatiles were removed in vacuo
  6. customthe residue was partitioned between ethyl acetate and water
  7. customThe organics were separated
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customthe volatiles were removed in vacuo
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with a stepwise gradient of iso-hexanes/ethyl acetate 1:0 to 7:3

Quellen und Nachweise

ORD-Eintrag
ord-d1b5029c87cf4757937aeaf6ef8a9d31
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145441B2

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