2-Ketobutyric acid methyl ester → Methyl 2-[3-(1,3-dioxolan-2-yl)-2-fluoro-4-pyridinyl]-2-hydroxybutanoate

HRID 47357

반응식

HRID 47357 반응식
C([Li])CCC.[O:6]1[CH2:10][CH2:9][O:8][CH:7]1[C:11]1[C:12]([F:18])=[N:13][CH:14]=[CH:15][C:16]=1I.[O:19]=[C:20]([CH2:25][CH3:26])[C:21]([O:23][CH3:24])=[O:22].O.C1COCC1>CCCCCC.C1COCC1>[O:6]1[CH2:10][CH2:9][O:8][CH:7]1[C:11]1[C:12]([F:18])=[N:13][CH:14]=[CH:15][C:16]=1[C:20]([OH:19])([CH2:25][CH3:26])[C:21]([O:23][CH3:24])=[O:22]

참가 물질

7

반응물 4

HCID 5451272-Ketobutyric acid methyl esterHCID 21881883Oxolane--water (1/1)HCID 227449983-(1,3-Dioxolan-2-yl)-2-fluoro-4-iodopyridineHCID 178418339Butyllithium

생성물 1

HCID 22745040Methyl 2-[3-(1,3-dioxolan-2-yl)-2-fluoro-4-pyridinyl]-2-hydroxybutanoate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매

실험 절차

6.9 ml (11 mmol) of 1.6M butyllithium in hexane are added dropwise to a solution, stirred at −78° C. under an argon atmosphere, of 3.1 g (11 mmol) of 3-(1,3-dioxolan-2-yl)-2-fluoro-4-iodopyridine in 100 ml of THF. The reaction mixture is then stirred for 10 minutes at −78° C. before the dropwise addition of a solution of 1.5 g (13 mmol) of methyl 2-oxo-butyrate in 20 ml of THF. The mixture is stirred for 3 hours at −78° C., hydrolysed with a mixture of water/THF, and decanted. The aqueous phase is extracted 3 times with 50 ml of ethyl acetate each time, and the combined organic phases are dried over magnesium sulphate and then concentrated. The expected product is obtained by purification of the residue by chromatography over silica (eluant: dichloromethane/acetone 95/5).

후처리

  1. customdecanted
  2. extractionThe aqueous phase is extracted 3 times with 50 ml of ethyl acetate each time
  3. dry with materialthe combined organic phases are dried over magnesium sulphate
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-9eab1e4ca5d14b6daf542e4f10225a96
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06699876B2

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