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

반응식

HRID 226385 반응식
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

참가 물질

8

반응물 4

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

생성물 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

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매2회HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

반응 조건

온도
4 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7c88d9cee2534b6ca1e1e09d580164f5
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557127B2

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