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

HRID 1184459Notes

Reaction equation

HRID 1184459 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 294 (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 (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), and brine (50 mL), dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo to provide the title compound as a yellow oil (1.90 g, 5.70 mmol, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 9H) 2.28 (s, 3H) 2.75 (d, J=4.55 Hz, 3H) 2.79-2.87 (m, 4H) 3.42-3.52 (m, 4H) 7.03 (d, J=8.34 Hz, 1H) 7.62 (dd, J=8.34, 2.27 Hz, 1H) 7.64-7.69 (m, 1H) 8.26 (q, J=4.46 Hz, 1H). 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), and brine (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. washrinsed with EtOAc
  6. customdried in vacuo

Sources & evidence

ORD record
ord-9047d014b47c48dcb0354b966a7d9c9f
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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