Ethyl Acetate → (S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide

HRID 455691노트

반응식

HRID 455691 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH2:36][O:37][CH3:38])=[C:6]([C@@:8]([C:21]2[CH:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]([F:33])[C:22]=2[Cl:34])([NH:14][S@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[C:9](OCC)=[O:10])[CH:7]=1.CC(C[AlH]CC(C)C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].CCOC(C)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH2:36][O:37][CH3:38])=[C:6]([C@:8]([NH:14][S@:15]([C:17]([CH3:18])([CH3:19])[CH3:20])=[O:16])([C:21]2[CH:26]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:24]=[C:23]([F:33])[C:22]=2[Cl:34])[CH2:9][OH:10])[CH:7]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydride3회HCID 9855836Potassium sodium tartarateHCID 86658387(S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate

생성물 1

HCID 67440021(S)-N-((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide수율 57.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (S)-ethyl 2-(5-bromo-2-(methoxymethoxy)phenyl)-2-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-((S)-1,1-dimethylethylsulfinamido)acetate (3.56 g, 5.59 mmol) in THF (60 mL) was cooled to 0° C. and treated drop wise with DIBAL (1M in THF) (22.36 mL, 22.36 mmol) under nitrogen atmosphere. After 1 h additional 10 mL DIBAL solution were added at RT. After 12 h at RT additional 10 mL DIBAL solution were added. After 30 min aqueous saturated solution of potassium sodium tartrate was added, followed by EtOAc. The reaction mixture was allowed to stir vigorously for 1 h. The organic phase was separated, washed with aqueous saturated solution of potassium sodium tartrate and dried over MgSO4. The solvent was removed under reduced pressure and the crude material was purified by silica gel chromatography (20-100% EtOAc/hexane) to provide 1.90 g of (S)—N—((S)-1-(5-bromo-2-(methoxymethoxy)phenyl)-1-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-2-hydroxyethyl)-2-methylpropane-2-sulfinamide.

후처리

  1. customThe organic phase was separated
  2. washwashed with aqueous saturated solution of potassium sodium tartrate
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed under reduced pressure
  5. customthe crude material was purified by silica gel chromatography (20-100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-9af7af164d6c4cc482ce20f08374690c
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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