Lithium diisopropylamide → 2-(4-Fluorophenyl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-3-hydroxypropionic acid methyl ester

HRID 7636

반응식

HRID 7636 반응식
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:12][CH:11]=1.[CH3:21][S:22][C:23]1[N:28]=[C:27]([CH:29]=[O:30])[CH:26]=[CH:25][N:24]=1>C1COCC1>[CH3:20][O:19][C:17](=[O:18])[CH:16]([C:13]1[CH:12]=[CH:11][C:10]([F:9])=[CH:15][CH:14]=1)[CH:29]([C:27]1[CH:26]=[CH:25][N:24]=[C:23]([S:22][CH3:21])[N:28]=1)[OH:30]

참가 물질

5

반응물 3

HCID 2724682Lithium diisopropylamideHCID 2733233Methyl 2-(4-fluorophenyl)acetateHCID 154070082-Methylsulfanylpyrimidine-4-carbaldehyde

생성물 1

HCID 129914022-(4-Fluorophenyl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-3-hydroxypropionic acid methyl ester수율 76%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a cold (−78° C.) solution of lithium diisopropylamide (21.4 mL of 2M solution in THF, 42.8 mmol) in THF (70 mL) is added dropwise a solution of methyl 4-fluorophenyl-acetate (6.0 g, 35.7 mmol) in THF (30 mL). The solution is stirred for 1 hour at −78° C. after which a solution of 2-methylsulfanyl-pyrimidine-4-carbaldehyde, 1, (6.0 g, 39.3 mmol) in THF (30 mL) is added dropwise to the reaction mixture. Stirring is continued for 45 minutes at −78° C. then the reaction is quenched by pouring the reaction solution into aqueous saturated NH4Cl. The aqueous phase is extracted with ethyl acetate. The organic phases combined, dried (MgSO4), filtered, and concentrated in vacuo. The crude residue is purified over silica (33% EtOAc/hexanes) to afford 8.7 g (76%) of the desired product as a mixture (1:1) of diastereomers.

후처리

  1. additionis added dropwise to the reaction mixture
  2. customthe reaction is quenched
  3. additionby pouring the reaction solution into aqueous saturated NH4Cl
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue is purified over silica (33% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-b695f5fa5646402185bd99e6f5509a2f
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087615B2

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