Hydrochloric Acid → tert-butyl (3R)-3-({3-chloro-5-[(1Z)-3-ethoxy-2-fluoro-3-oxo-1-propen-1-yl]-2-pyridinyl}amino)-1-piperidinecarboxylate

HRID 226385

Reaktionsgleichung

Reaktionsgleichung von HRID 226385
COP([CH:7]([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(OC)=O.[Mg+2].[Br-].[Br-].[Cl:17][C:18]1[C:19]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]2)=[N:20][CH:21]=[C:22]([CH:24]=O)[CH:23]=1.Cl>C1COCC1.CCOC(C)=O.CCN(CC)CC>[Cl:17][C:18]1[C:19]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]2)=[N:20][CH:21]=[C:22](/[CH:24]=[C:7](\[F:13])/[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:23]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 82241Magnesium BromideHCID 12696184Ethyl (dimethoxyphosphoryl)(fluoro)acetateHCID 86603692tert-butyl (3R)-3-[(3-chloro-5-formyl-2-pyridinyl)amino]-1-piperidinecarboxylate

Produkt 1

HCID 86603685tert-butyl (3R)-3-({3-chloro-5-[(1Z)-3-ethoxy-2-fluoro-3-oxo-1-propen-1-yl]-2-pyridinyl}amino)-1-piperidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
4 °C

Versuchsvorschrift

The mixture of ethyl (dimethoxyphosphoryl)(fluoro)acetate (2.51 mL), MgBr2 (2.73 g), Et3N (1.89 mL) in THF (45 mL) was stirred at 3-5° C. for 1 hr and to the mixture was dropwise added a solution of tert-butyl (3R)-3-[(3-chloro-5-formyl-2-pyridinyl)amino]-1-piperidinecarboxylate (3.0 g) in THF (21 mL) at 3-5° C. The reaction mixture was stirred at same temperature for 2.5 hrs. The reaction mixture was poured into a mixture of AcOEt and ice-water and the mixture was adjusted to pH 3.5 with 1N-HCl. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel using a mixture of AcOEt and hexane (1:2 v/v) as an eluant. The eluted fractions containing the desired product were collected and evaporated in vacuo to give tert-butyl (3R)-3-({3-chloro-5-[(1Z)-3-ethoxy-2-fluoro-3-oxo-1-propen-1-yl]-2-pyridinyl}amino)-1-piperidinecarboxylate (3.38 g).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at same temperature for 2.5 hrs
  2. washThe separated organic layer was washed with water
  3. dry with materialdried over magnesium sulfate
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography on silica gel using
  6. additiona mixture of AcOEt and hexane (1:2 v/v) as an eluant
  7. additionThe eluted fractions containing the desired product
  8. customwere collected
  9. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-7c88d9cee2534b6ca1e1e09d580164f5
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557127B2

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