Sodium hydride → (4-Methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate

HRID 2262506노트

반응식

HRID 2262506 반응식
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH:5]1[CH2:10][OH:11].[N+](C1C=CC([O:21][C:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)=O)=CC=1)([O-])=O.C([O-])(O)=O.[Na+]>C1COCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([N:27]2[CH2:26][CH2:25][N:24]([C:22]([O:11][CH2:10][CH:5]3[CH2:6][O:7][CH2:8][CH2:9][N:4]3[CH3:3])=[O:21])[CH2:29][CH2:28]2)=[CH:35][CH:34]=1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 23541157(4-Methylmorpholin-3-yl)methanolHCID 595944824-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester2회

생성물 1

HCID 42634519(4-Methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate수율 243.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

NaH (60% in oil, prewashed with hexane; 0.91 g, 22.9 mmol) was suspended in anhydrous THF (25 mL) under nitrogen and cooled to 0° C. with stirring. A solution of (4-methyl-morpholin-3-yl)-methanol (1.00 g, 2.62 mmol) in THF (25 mL) was added dropwise. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 3.16 g, 9.15 mmol) was added and the reaction mixture was stirred overnight at room temperature. A saturated aqueous solution of NaHCO3 (10 mL) was added and the solvents were removed in vacuo. The residue was partitioned between water and EtOAc and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with sat aq NaHCO3 (3×100 mL), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A) eluting with 1% MeOH in DCM to give (4-methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate (2.15 g, 83%) as a white solid.

후처리

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. customthe solvents were removed in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organic extracts were washed with sat aq NaHCO3 (3×100 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvents were removed in vacuo
  8. customThe residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A)
  9. washeluting with 1% MeOH in DCM

출처 및 근거

ORD 기록
ord-1ef143343584450bade658ce87fe47ad
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07851471B2

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