4-Methylmorpholine → Tert-butyl 4-(4-(ethylcarbamoyl)-2-methylphenyl)piperazine-1-carboxylate

HRID 1184460Notes

Reaction equation

HRID 1184460 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]([OH:20])=O)=[CH:16][C:15]=2[CH3:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:25]([NH2:27])[CH3:26].Cl.C(N=C=NCCCN(C)C)C.O.N1(O)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O>[CH2:25]([NH:27][C:18]([C:17]1[CH:21]=[CH:22][C:14]([N:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[C:15]([CH3:23])[CH:16]=1)=[O:20])[CH3:26]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 11198Ethylamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 186632454-(4-(Tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid

Product 1

HCID 58324366Tert-butyl 4-(4-(ethylcarbamoyl)-2-methylphenyl)piperazine-1-carboxylateYield 99.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid 294 (0.866 g, 2.70 mmol), ethanamine hydrochloride (0.264 g, 3.24 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.777 g, 4.05 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (0.621 g, 4.05 mmol) were suspended in DMF (3.68 mL) and 4-methylmorpholine (1.486 mL, 13.52 mmol) was added. The reaction mixture was stirred at ambient temperature for 2 h, diluted with water (50 mL), and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with 1N HCl(aq., 25 mL), NaHCO3 (sat. aq., 25 mL), water (25 mL), and brine (25 mL), dried over MgSO4, concentrated in vacuo, and dried under vacuum to afford the title compound as a white solid (0.9327 g, 2.68 mmol, 99% yield). 1H NMR (DMSO-d6, 400 MHz): δ=8.24 (t, J=5.4 Hz, 1H), 7.66 (d, J=1.8 Hz, 2H), 7.03 (d, J=8.3 Hz, 1H), 3.42-3.52 (m, 4H), 3.20-3.27 (m, 2H), 2.78-2.87 (m, 4H), 2.28 (s, 3H), 1.43 (s, 9H), 1.10 ppm (t, J=7.2 Hz, 3H). ESI-MS: m/z 348.4 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×75 mL)
  2. washThe combined organic extracts were washed with 1N HCl(aq., 25 mL), NaHCO3 (sat. aq., 25 mL), water (25 mL), and brine (25 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customdried under vacuum

Sources & evidence

ORD record
ord-49f84868982247b8a7eecc2fa572b360
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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