Ethyl orthoformate → benzyl 4-[(1R,2S)-2-(2-{[3-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]oxy}ethyl)cyclopropyl]piperidine-1-carboxylate

HRID 1850751Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1850751
[NH2:1][C:2]1[CH:3]=[C:4]([CH3:30])[C:5]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:16][CH2:15]2)=[N:6][CH:7]=1.[N-:31]=[N+:32]=[N-:33].[Na+].[CH:35](OCC)(OCC)OCC>C(O)(=O)C>[CH3:30][C:4]1[C:5]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:21])[CH2:16][CH2:15]2)=[N:6][CH:7]=[C:2]([N:1]2[CH:35]=[N:33][N:32]=[N:31]2)[CH:3]=1

Komponenten

5

Edukt 3

HCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 70856037benzyl 4-((1R,2S)-2-{2-[(5-amino-3-methylpyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

Produkt 1

HCID 66563379benzyl 4-[(1R,2S)-2-(2-{[3-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]oxy}ethyl)cyclopropyl]piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of benzyl 4-((1R,2S)-2-{-[(5-amino-3-methylpyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate (1.20 g, 2.93 mmol) in acetic acid (50 mL) was added sodium azide (762 mg, 11.72 mmol) followed by triethyl orthoformate (1.95 mL, 11.72 mmol) and the resulting solution was heated to 60° C. and stirred for 3 hours. The volatiles were removed in vacuo and the residue was partitioned between NaHCO3 and ethyl acetate. The aqueous was again extracted with ethyl acetate (100 mL). The organics were combined, washed by brine, dried on sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified on Biotage column (40 M+ silica gel) using a gradient eluant of 0-100% ethyl acetate in hexane (800 ml) to afford the title compound. LC/MS (m/z): 463 (M+H)+.

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between NaHCO3 and ethyl acetate
  3. extractionThe aqueous was again extracted with ethyl acetate (100 mL)
  4. washwashed by brine
  5. customdried on sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue was purified on Biotage column (40 M+ silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-5f2c0ec0d9a94b4e8071035787d3341a
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08957062B2

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