4-Methylmorpholine → Tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylate

HRID 44323Notes

Reaction equation

HRID 44323 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][C:15]=2[CH3:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.Cl.[CH2:28]([N:30]=C=NCCCN(C)C)C.O.N1(O)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O>[CH3:23][C:15]1[CH:16]=[C:17]([C:18](=[O:19])[NH:30][CH3:28])[CH:21]=[CH:22][C:14]=1[N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9][CH2:10]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 186632454-(4-(Tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid

Product 1

HCID 59416789Tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylateYield 91.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

To a suspension of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid (2.0 g, 6.24 mmol), methanamine hydrochloride (0.506 g, 7.49 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.795 g, 9.36 mmol), and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (1.434 g, 9.36 mmol) in DMF (Volume: 8.5 mL) was added 4-methylmorpholine (3.43 mL, 31.2 mmol) at 23° C. The reaction was stirred at 23° C. for 2 hr. The reaction mixture was diluted with water (100 mL) and the product was extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with 1N HCl (50 mL), saturated NaHCO3 (50 mL), H2O (50 mL), brine (50 mL) dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo to provide tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylate (1.90 g, 5.70 mmol, 91% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 9 H) 2.28 (s, 3 H) 2.75 (d, J=4.55 Hz, 3 H) 2.79-2.87 (m, 4 H) 3.42-3.52 (m, 4 H) 7.03 (d, J=8.34 Hz, 1 H) 7.62 (dd, J=8.34, 2.27 Hz, 1 H) 7.64-7.69 (m, 1 H) 8.26 (q, J=4.46 Hz, 1 H). ESI-MS: m/z 334.3 (M+H)+.

Workup

  1. extractionthe product was extracted with EtOAc (3×100 mL)
  2. washwashed with 1N HCl (50 mL), saturated NaHCO3 (50 mL), H2O (50 mL), brine (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. washrinsed with EtOAc
  6. customdried in vacuo

Sources & evidence

ORD record
ord-a4cb92fbf6474e22af9477b9f61facad
Source dataset
uspto-grants-2013_09
Patent number
US08541417B2

Reaction notes

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