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

HRID 2262506Notes

Reaction equation

HRID 2262506 reaction equation
[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

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 23541157(4-Methylmorpholin-3-yl)methanolHCID 595944824-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester2×

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-1ef143343584450bade658ce87fe47ad
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

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