2-Methylpiperidine → Ethyl 4-(2-methylpiperidin-1-yl)-3-nitrobenzoate

HRID 219782

Reaction equation

HRID 219782 reaction equation
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][NH:18]1>CN(C=O)C.O>[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][N:18]1[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]

Participants

5

Reactant 2

HCID 79742-MethylpiperidineHCID 21277355Ethyl 4-fluoro-3-nitrobenzoate

Product 1

HCID 67400209Ethyl 4-(2-methylpiperidin-1-yl)-3-nitrobenzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 1 g; 4.69 mmol; 1 eq.) and 2-methylpiperidine (1.395 g; 14.07 mmol; 3 eq.) in DMF (4 mL) was heated to 50° C. for 3 hours. The reaction was then allowed to return to RT and diluted with water. It was extracted with EtOAc and the organic phase was dried over sodium sulfate and concentrated in vacuo, affording ethyl 4-(2-methylpiperidin-1-yl)-3-nitrobenzoate as a yellow oil. The residue was taken up in THF (10 mL) and lithium hydroxide (561.73 mg; 23.46 mmol; 5 eq.) was added followed by water (10 mL). The reaction mixture was stirred at RT for 16 hours. It was concentrated and the residue was diluted with water and washed with Et2O. The aqueous layer was acidified to pH 5 with acetic acid. It was extracted with Et2O and the organic phase was dried over magnesium sulfate and concentrated, affording the title compound as a yellow solid (1.17 g, 94%). 1H NMR: (DMSO-d6, 300 MHz) δ 13.07 (s, 1H), 8.23-8.22 (d, J=2.13 Hz, 1H), 8.04-8 (dd, J=8.96 Hz, J=2.28 Hz, 1H), 7.44-7.41 (d, J=8.88 Hz, 1H), 3.64-3.60 (m, 1H), 3.25-3.17 (m, 1H), 2.90-2.84 (m, 1H), 1.82-1.43 (m, 6H), 1.06-1.04 (d, J=6.43 Hz, 3H). LC/MS (Method A): 265.0 (M+H)+; 263.0 (M−H)−.

Workup

  1. customto return to RT
  2. extractionIt was extracted with EtOAc
  3. dry with materialthe organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-677fe82040674e12b4013cc18fab207c
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Linked notes

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