Acetic Acid → tert-Butyl 4-(2-chloro-5-nitrophenylamino)piperidine-1-carboxylate

HRID 424578Notes

Reaction equation

HRID 424578 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].O=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.O.[OH-].[Na+]>[Cl:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH:4][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 226912-Chloro-5-nitroanilineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 59144150tert-Butyl 4-(2-chloro-5-nitrophenylamino)piperidine-1-carboxylateYield 61.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

A solution of 2-chloro-5-nitroaniline (1 g, 5.79 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.309 g, 11.59 mmol) in dichloroethane (15 mL) and acetic acid (0.995 mL, 17.38 mmol) was stirred at room temperature for 30 minutes. At this time, the reaction was treated with sodium triacetoxyborohydride (3.07 g, 14.49 mmol), and the resulting mixture was stirred over the weekend. Additional tert-butyl 4-oxopiperidine-1-carboxylate (2.309 g, 11.59 mmol), sodium triacetoxyborohydride (3.07 g, 14.49 mmol), and dichloroethane (15 mL) were added. Stirring was continued for 2 days. The mixture was then diluted with water and 1N sodium hydroxide (basified to pH 10) and then extracted with dichloromethane (3×). The combined organics were dried, filtered, concentrated, and then chromatographed in 1:19 ethyl acetate:hexanes, giving a yellow/orange foam (1.26 g, 61.1%). 1H NMR (DMSO-d6) δ 7.54 (d, J=8.7 Hz, 1H), 7.51 (d, J=2.4 Hz, 1H), 7.39 (dd, J=8.7, 2.4 Hz, 1H), 5.76-5.63 (m, 1H), 3.99-3.90 (m, 2H), 3.74-3.62 (m, 1H), 3.05-2.80 (m, 2H), 1.89-1.80 (m, 2H), 1.49-1.32 (m, 11H); ESI-MS (m/z, %): 378 (M+Na, 100), 356 (MH+, 40), 300 (62).

Workup

  1. stirringStirring
  2. extractionextracted with dichloromethane (3×)
  3. customThe combined organics were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed in 1:19 ethyl acetate

Sources & evidence

ORD record
ord-9d93192c63794b8ebf2f604ffb104d73
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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