Ammonium Chloride → 4-[2-(5-Bromo-2-chloro-pyridin-4-yl)-1-hydroxy-1-methyl-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1184716노트

반응식

HRID 1184716 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:24])[CH2:15][C:16]2[C:21]([Br:22])=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][Mg]Br.[NH4+].[Cl-]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]([OH:24])([CH3:25])[CH2:15][C:16]2[C:21]([Br:22])=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 25517Ammonium ChlorideHCID 866748944-[2-(5-Bromo-2-chloropyridin-4-yl)acetyl]piperidine-1-carboxylic acid tert-butyl esterHCID 178418573HCID 178418573, 화합물

생성물 1

HCID 866748994-[2-(5-Bromo-2-chloro-pyridin-4-yl)-1-hydroxy-1-methyl-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 4-[2-(5-bromo-2-chloro-pyridin-4-yl)-acetyl]-piperidine-1-carboxylic acid tert-butyl ester (9.80 g) in tetrahydrofuran (6 mL) is added drop wise to an ice cooled solution of methylmagnesium bromide (1.4 M in toluene/tetrahydrofuran 75:25,74 mL). The reaction mixture is stirred for 30 min, warmed to room temperature and stirred for 1 h. The mixture is poured onto aqueous NH4Cl solution and extracted with ethyl acetate. The combined extracts are dried over MgSO4 and concentrated in vacuo. Toluene is added to the residue and evaporated several times. Since the residue still contains a considerable amount of starting material, it is again treated with the Grignard reagent following the procedure described above. The crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0) to give the title compound. LC (method 6): tR=1.33 min; Mass spectrum (ESI+): m/z=433, 435 [M+H]+.

후처리

  1. stirringstirred for 1 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts are dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. additionToluene is added to the residue
  6. customevaporated several times
  7. additionis again treated with the Grignard reagent following the procedure
  8. customThe crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0)

출처 및 근거

ORD 기록
ord-502879d488ab4fc4b8b416f61312abd9
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669271B2

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