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

HRID 872202노트

반응식

HRID 872202 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>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

4

반응물 2

HCID 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 dropwise to an ice-cold solution of methyl magnesium bromide (1.4 mol/L in toluene/tetrahydrofuran 75:25; 74.0 mL). The reaction mixture is stirred for 30 min before the cooling bath is removed. After stirring the mixture at room temperature for 1 h, the mixture is poured into aqueous NH4Cl solution. The resulting mixture is extracted with ethyl acetate, and the combined extracts are dried (MgSO4) and concentrated. The residue containing significant amounts of starting material is azeotropically dried using toluene and resubmitted to the reaction conditions and work-up procedure described. 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. Mass spectrum (ESI+): m/z=433/435/437 (Cl+Br) [M+H]+.

후처리

  1. customis removed
  2. stirringAfter stirring the mixture at room temperature for 1 h
  3. additionthe mixture is poured into aqueous NH4Cl solution
  4. extractionThe resulting mixture is extracted with ethyl acetate
  5. dry with materialthe combined extracts are dried (MgSO4)
  6. concentrationconcentrated
  7. additionThe residue containing significant amounts of starting material
  8. customis azeotropically dried
  9. customresubmitted to the reaction conditions
  10. 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-10c3ddb07d554e7e91c58556bfbcd364
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975277B2

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