6-Bromo-2,3-dichloropyridine → 2-[(5,6-Dichloro-pyridin-2-yl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1895025노트

반응식

HRID 1895025 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([Cl:9])[N:3]=1.C([Mg]Cl)(C)C.[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C:23]1([CH:30]=[O:31])[CH2:27][CH2:28][CH3:29])=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C:23]1([CH:30]([C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([Cl:9])[N:3]=1)[OH:31])[CH2:27][CH2:28][CH3:29])=[O:21])([CH3:17])([CH3:18])[CH3:16]

참가 물질

5

반응물 3

HCID 467368346-Bromo-2,3-dichloropyridineHCID 866208602-Formyl-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418918HCID 178418918, 화합물

생성물 1

HCID 866208612-[(5,6-Dichloro-pyridin-2-yl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester수율 56.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a stirred solution of 2-bromo-5,6-dichloro-pyridine (0.500 g, 2.20 mmol) in THF (6 mL) at 0° C. and under nitrogen was added isopropylmagnesium chloride (1.21 mL of a 2 M solution in THF, 2.42 mmol) dropwise. After 2 hours, a solution of 2-formyl-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.317 g, 1.32 mmol) in THF (1 mL) was added to the reaction mixture dropwise. After 30 minutes, the reaction mixture was warmed to ambient temperature and stirred for one hour, then quenched by the addition of saturated aqueous NH4Cl (10 mL) and extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. Purification of the residue by chromatography (silica, 0 to 40% EtOAc in hexanes) gave 2-[(5,6-dichloro-pyridin-2-yl)-hydroxy-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.289 g, 0.745 mmol, 56%) as a yellow oil and as an inseparable mixture of diastereomers.

후처리

  1. waitAfter 30 minutes
  2. customquenched by the addition of saturated aqueous NH4Cl (10 mL)
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by chromatography (silica, 0 to 40% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-8c911c12a61241f88324f917ac16145f
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513425B2

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