Trifluoroacetic anhydride → Benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate

HRID 1184040

Reaktionsgleichung

Reaktionsgleichung von HRID 1184040
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[C:14]([C@@H:17]1[CH2:22][C@H:21]2[C@H:19]([CH2:20]2)[N:18]1[C:23](=[O:47])[C@@H:24]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:25]12[CH2:34][CH:29]3[CH2:30][CH:31]([CH2:33][C:27]([OH:35])([CH2:28]3)[CH2:26]1)[CH2:32]2)(=O)[NH2:15].C(OCC)(=O)C1C=CC=NC=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CO.O>[C:14]([C@@H:17]1[CH2:22][C@H:21]2[C@H:19]([CH2:20]2)[N:18]1[C:23](=[O:47])[C@@H:24]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[C:25]12[CH2:32][CH:31]3[CH2:30][CH:29]([CH2:28][C:27]([OH:35])([CH2:33]3)[CH2:26]1)[CH2:34]2)#[N:15]

Komponenten

8

Edukt 4

HCID 9845Trifluoroacetic anhydrideHCID 11430Potassium CarbonateHCID 69188Ethyl NicotinateHCID 86703401benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate

Produkt 1

HCID 86703399Benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamateAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Trifluoro acetic anhydride (41.36 gm) was added to a solution of [benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo-ethyl]carbamate of formula-XV (27 gm) and ethyl nicotinate (30.6 gm) in ethyl acetate at 0-5° C. After 6 hrs water was added to the reaction. Organic phase was washed with 2N HCl solution, dried and concentrated. The crude compound obtained was dissolved in methanol, hydrolyzed with aqueous potassium carbonate (112 gm of K2CO3 in 228 ml water) for 2 hrs at 25° C. Solvent was distilled off from the reaction mass and aqueous phase extracted with ethyl acetate. Organic phase was dried and evaporated and the solid obtained was purified in THF to yield 20.8 gm (80%) of the desired product. M.P: 148-150° C., HPLC Purity: 99.5% (A), H1NMR (300 MHz, CDCl3): 1.06-1.09 (m, 2H), 1.45-1.9 (m, 12H), 2.25 (m, 2H), 2.33-2.38 (dd, 1H), 2.52-2.54 (m, 1H), 3.82-3.84 (dd, 1H), 4.5 (d, 1H), 4.99-5.04 (dd, 1H), 5.08 (s, 2H), 5.59-5.63 (d, 1H), 7.32-7.63 (m, 5H).

Aufarbeitung

  1. washOrganic phase was washed with 2N HCl solution
  2. customdried
  3. concentrationconcentrated
  4. customThe crude compound obtained
  5. distillationSolvent was distilled off from the reaction mass and aqueous phase
  6. extractionextracted with ethyl acetate
  7. customOrganic phase was dried
  8. customevaporated
  9. customthe solid obtained
  10. customwas purified in THF

Quellen und Nachweise

ORD-Eintrag
ord-cbf4916f3a504e668b0bf464fea507c9
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08664443B2

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