Sodium hydride → HCID 42634186, compound

HRID 2262493Notes

Reaction equation

HRID 2262493 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][O:5][C@H:4]([CH2:8][OH:9])[CH2:3]1.[H-].[Na+].[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>C1COCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([N:27]2[CH2:26][CH2:25][N:24]([C:22]([O:9][CH2:8][C@H:4]3[O:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]3)=[O:21])[CH2:29][CH2:28]2)=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 40152302(S)-4-Methyl-2-(hydroxymethyl)morpholine2×HCID 595944824-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester2×

Product 1

HCID 42634186HCID 42634186, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-(4-Methyl-morpholin-2-yl)-methanol (Intermediate 10; 100 mg, 0.76 mmol) was added to a suspension of NaH (60% dispersion in oil; 90.0 mg, 2.28 mmol) in anhydrous THF (7 mL) and stirred under nitrogen for 30 min. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 314 mg, 0.91 mmol) was added and the reaction mixture was stirred at room temperature for 48 h. The reaction mixture was filtered through celite and the solid washed with THF (10 mL). The filtrates were combined and the solvent removed in vacuo. The residue was purified by column chromatography (normal phase silica, 5 g Isolute-Si column, gradient 1-5% MeOH in DCM) and the solvents were removed in vacuo to give [(2S)-4-methylmorpholin-2-yl]methyl 4-(4-fluorophenyl)-piperazine-1-carboxylate (130 mg, 51%) as a light brown solid.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 48 h
  2. filtrationThe reaction mixture was filtered through celite
  3. washthe solid washed with THF (10 mL)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by column chromatography (normal phase silica, 5 g Isolute-Si column, gradient 1-5% MeOH in DCM)
  6. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-6df8b86826f54fbcb5672cab60daba52
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

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