tert-Butanol → benzyl (2S,5R)-5-((tert-butoxycarbonyl)amino)-2-methylpiperidine-1-carboxylate

HRID 2367419Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2367419
[CH3:1][C@H:2]1[N:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:6][C@@H:5](C(O)=O)[CH2:4][CH2:3]1.[C:21]([OH:25])([CH3:24])([CH3:23])[CH3:22].C([N:28]([CH2:31]C)CC)C.P(N=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=[O:34]>>[C:12]1([CH2:11][O:10][C:8]([N:7]2[CH2:6][C@H:5]([NH:28][C:31]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:34])[CH2:4][CH2:3][C@@H:2]2[CH3:1])=[O:9])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Komponenten

5

Edukt 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 51357693(3S,6R)-1-((benzyloxy)carbonyl)-6-methylpiperidine-3-carboxylic acid

Produkt 1

HCID 51354040benzyl (2S,5R)-5-((tert-butoxycarbonyl)amino)-2-methylpiperidine-1-carboxylateAusbeute 35,2 %

Versuchsvorschrift

cis-6-methyl-1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinecarboxylic acid (2.62 g, 9.45 mmol) was dissolved in t-butyl alcohol (20 mL, 212 mmol) (anhydrous) in a 40 mL vial. Triethylamine (1.975 mL, 14.17 mmol) was added, followed by the slow addition of diphenyl azidophosphate (dppa) (1.87 mL, 8.65 mmol) at room temperature. The reaction was stirred at room temperature for 30 minutes, and then heated at 100° C. overnight. The reaction mixture was concentrated, and then redissolved with 150 mL of EtOAc. The resulting organic mixture was washed with water (50 mL), brine, dried (Na2SO4), filtered, and concentrated. The resulting clear oil was purified in 50 g Biotage SNAP column with gradient of 0 to 50% of EtOAc in Hexane over 40 minutes to afford the title compound (1.06 g) as a clear oil. LC-MS (ES) m/z=349 [M+H]+.

Aufarbeitung

  1. temperatureheated at 100° C. overnight
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionredissolved with 150 mL of EtOAc
  4. washThe resulting organic mixture was washed with water (50 mL), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting clear oil was purified in 50 g Biotage SNAP column with gradient of 0 to 50% of EtOAc in Hexane over 40 minutes

Quellen und Nachweise

ORD-Eintrag
ord-a86890251bd84838a54287aad230ff6c
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697685B2

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