Acetic Acid → (S)-Tert-butyl 4-methyl-4-(3-methylpiperazin-1-YL)piperidine-1-carboxylate

HRID 2178778Notes

Reaction equation

HRID 2178778 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2([CH3:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:10][C@@H:9]1[CH3:28])C1C=CC=CC=1.C(O)(=O)C>CO>[CH3:27][C:14]1([N:11]2[CH2:12][CH2:13][NH:8][C@@H:9]([CH3:28])[CH2:10]2)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 59017283t-Butyl 4-[(3S)-4-Benzyl-3-methylpiperazin-1-yl]-4-methylpiperidine-1-carboxylate

Product 1

HCID 17759466(S)-Tert-butyl 4-methyl-4-(3-methylpiperazin-1-YL)piperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of t-butyl 4-[(3S)-4-benzyl-3-methylpiperazin-1-yl]-4-methylpiperidine-1-carboxylate (45.5 g, 0.118 mol) in methanol (320 mL) and acetic acid (35 mL, ˜5 equiv) in a 2.25 L Parr bottle was charged with H2 to 60 psi and the mixture shaken for 18 hr. The reaction mixture was filtered through a pad of Celite and the pad was washed with methanol. The filtrate was concentrated under vacuum. The residual oil was dissolved in DCM (500 mL) and washed with aqueous sodium hydroxide (300 mL). The aqueous phase was back-extracted with methylene chloride (200 mL). The combined organic solution was washed with brine (500 mL), dried with sodium sulfate and the solvent was removed under vacuum to give 35 g (100%) of product as a pale yellow viscous oil that slowly crystallized. 1H NMR (400 MHz, CDCl3) δ (ppm) 3.44 (m, 2H), 3.36 (m, 2H), 2.97 (dt, 1H), 2.84 (dd, 1H), 2.78 (m, 1H), 2.71 (brd, 2H), 2.16 (dt, 1H), 1.81 (t, 2H), 1.76 (m, 1H), 1.45 (s, 9H), 1.34 (m, 3H), 1.03 (d, 3H), 0.90 (s, 3H); MS (EI) 298.2 (M+1).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite
  2. washthe pad was washed with methanol
  3. concentrationThe filtrate was concentrated under vacuum
  4. dissolutionThe residual oil was dissolved in DCM (500 mL)
  5. washwashed with aqueous sodium hydroxide (300 mL)
  6. extractionThe aqueous phase was back-extracted with methylene chloride (200 mL)
  7. washThe combined organic solution was washed with brine (500 mL)
  8. dry with materialdried with sodium sulfate
  9. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-e21d4524478b475bb7a8bf5cfd8a0ed7
Source dataset
uspto-grants-2015_06
Patent number
US09067921B2

Reaction notes

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