Acetic Acid → (2R,5S)-tert-butyl 2-methyl-5-(((R)-3-methylmorpholino)methyl)piperazine-1-carboxylate

HRID 1475482Notes

Reaction equation

HRID 1475482 reaction equation
C(O)(=O)C.[C:5]([O:9][C:10]([N:12]1[CH2:17][C@H:16]([CH2:18][N:19]2[CH2:24][CH2:23][O:22][CH2:21][C@H:20]2[CH3:25])[N:15](CC2C=CC=CC=2)[CH2:14][C@H:13]1[CH3:33])=[O:11])([CH3:8])([CH3:7])[CH3:6]>CCO.[Pd]>[C:5]([O:9][C:10]([N:12]1[CH2:17][C@H:16]([CH2:18][N:19]2[CH2:24][CH2:23][O:22][CH2:21][C@H:20]2[CH3:25])[NH:15][CH2:14][C@H:13]1[CH3:33])=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 86724030(2R,5S)-4-Benzyl-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 70980298(2R,5S)-tert-butyl 2-methyl-5-(((R)-3-methylmorpholino)methyl)piperazine-1-carboxylateYield 95.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Pd/C (33 g) and acetic acid (220 mL) were added to a solution of (2R,5S)-4-benzyl-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (41.3 g, 102 mmol) in EtOH (300 mL). The mixture was stirred under H2 (1 atmosphere) at room temperature for 18 h. The reaction mixture was then filtered through a pad of Celilte to remove the catalyst and the solvent was removed in vacuo. The crude material was partitioned between saturated aqueous NaHCO3 and DCM and the product extracted with DCM (3×). The organic phase was dried over MgSO4, filtered and concentrated in vacuo to give the title compound (30.5 g) as a pale yellow oil. 1H NMR (CDCl3): 4.43-3.87 (1H, m), 3.78 (1H, d), 3.73-3.55 (3H, m), 3.32 (1H, dd), 3.22 (1H, dd), 3.16-2.93 (3H, m), 2.93-2.72 (1H, m), 2.55-2.35 (2H, m), 2.35-2.15 (2H, m), 1.89 (1H, dd), 1.45 (9H, s), 1.26 (3H, d), 0.96 (3H, d).

Workup

  1. filtrationThe reaction mixture was then filtered through a pad of Celilte
  2. customto remove the catalyst
  3. customthe solvent was removed in vacuo
  4. customThe crude material was partitioned between saturated aqueous NaHCO3 and DCM
  5. extractionthe product extracted with DCM (3×)
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3c5aed64360044fda33acce84c0578ff
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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