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

HRID 1184716ノート

反応式

HRID 1184716 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-502879d488ab4fc4b8b416f61312abd9
出典データセット
uspto-grants-2014_03
特許番号
US08669271B2

反応ノート

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