Water → Tert-butyl 4-[3-(propionylamino)phenyl]-1-piperidinecarboxylate

HRID 1832220Notes

Reaction equation

HRID 1832220 reaction equation
[C:1](Cl)(=[O:4])[CH2:2][CH3:3].[NH2:6][C:7]1[CH:8]=[C:9]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:10]=[CH:11][CH:12]=1.O>C1COCC1>[C:1]([NH:6][C:7]1[CH:8]=[C:9]([CH:13]2[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]2)[CH:10]=[CH:11][CH:12]=1)(=[O:4])[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 62324Propionyl chlorideHCID 22049268tert-Butyl 4-(3-aminophenyl)piperidine-1-carboxylate

Product 1

HCID 22049473Tert-butyl 4-[3-(propionylamino)phenyl]-1-piperidinecarboxylateYield 104.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Propionyl chloride (5.53 g, 0.0597 mol) was added dropwise to a solution of tert-butyl 4-(3-aminophenyl)-1-piperidinecarboxylate (15.0 g, 0.0543 mol) and TEA (16.5 g, 0.163 mol) in THF (200 mL) and the mixture was stirred at room temperature for 3 h. Water (50 mL) was added to the reaction mixture, the aqueous layer was extracted with CH2Cl2 (3×100 mL), and the combined organic extracts were washed with brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/EtOAc (10:1) to afford the product (18.8 g, 99%). 1H NMR (400 MHz, CDCl3) δ 7.48 (s, 1H) 7.34–7.21 (m, 3H), 6.93 (d, 1H, J=7.4 Hz), 2.77 (t, 2H, J=11.5 Hz), 2.68–2.58 (m, 1H), 2.38 (q, 2H, J=7.6 Hz), 1.87–1.67 (m, 4H), 1.67–1.54 (m, 2H), 1.48 (s, 9H), 1.25 (t, 3H, J=7.5 Hz); ESMS m/e: 333.4 (M+H)+.

Workup

  1. extractionthe aqueous layer was extracted with CH2Cl2 (3×100 mL)
  2. washthe combined organic extracts were washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-421dc3d39e8b40e69b90906c1289b02c
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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