Sodium hydride → [(2S)-4-methylmorpholin-2-yl]methyl 4-phenyl-piperazine-1-carboxylate

HRID 2262491Notes

Reaction equation

HRID 2262491 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+].[C:12]1([N:18]2[CH2:23][CH2:22][N:21]([C:24](OC3C=CC([N+]([O-])=O)=CC=3)=[O:25])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[C:12]1([N:18]2[CH2:19][CH2:20][N:21]([C:24]([O:9][CH2:8][C@H:4]3[O:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]3)=[O:25])[CH2:22][CH2:23]2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 40152302(S)-4-Methyl-2-(hydroxymethyl)morpholine2×HCID 595944814-Nitrophenyl 4-phenylpiperazine-1-carboxylate2×

Product 1

HCID 42634185[(2S)-4-methylmorpholin-2-yl]methyl 4-phenyl-piperazine-1-carboxylateYield 20.6%

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-Nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 300 mg, 0.92 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) then by reverse phase HPLC(YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 20% to 100% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water). The pure product was taken up in DCM (5 mL), filtered, and dried in vacuo to give [(2S)-4-methylmorpholin-2-yl]methyl 4-phenyl-piperazine-1-carboxylate (50 mg, 20%) as a colourless gum.

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. customby reverse phase HPLC(YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 20% to 100% (over 7 min)
  7. custom100% (3 min) MeOH in 10% MeOH/water
  8. filtrationfiltered
  9. customdried in vacuo

Sources & evidence

ORD record
ord-7a13aed209ed44dab5ec9daf98247fef
Source dataset
uspto-grants-2010_12
Patent number
US07851471B2

Reaction notes

Loading…