Acetic Acid → tert-Butyl 4-(3-fluoroanilino)piperidine-1-carboxylate

HRID 883760Notes

Reaction equation

HRID 883760 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[F:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[F:15][C:16]1[CH:17]=[C:18]([NH:19][CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)[CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 97423-FluoroanilineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 23137591tert-Butyl 4-(3-fluoroanilino)piperidine-1-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (1.91 g, 9.53 mmol), 3-fluoroaniline (1.06 g, 9.53 mmol) and acetic acid (0.55 ml, 9.53 mmol) in 1,2-DCE (50 ml) was stirred at room temperature overnight. Sodium tri(acetoxy)borohydride (2.82 g, 13.3 mmol) was then added and the reaction mixture was stirred for 8 h, then allowed to stand at room temperature. The reaction mixture was diluted with DCM and washed with NaHCO3 solution, dried over MgSO4 and then concentrated to give the product which was purified by column chromatography. Elution with 0-40% EtOAc/pentane gave the title compound as a white solid (2.3 g). δH (CDCl3, 250 MHz) 7.08 (1H, q), 6.35 (3H, m), 4.04 (1H, br s), 3.65 (1H, br s), 3.38 (1H, m), 2.92 (2H, m), 2.02 (2H, m), 1.47 (9H, s), 1.34 (2H, m).

Workup

  1. stirringthe reaction mixture was stirred for 8 h
  2. customto stand at room temperature
  3. washwashed with NaHCO3 solution
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give the product which
  7. customwas purified by column chromatography
  8. washElution with 0-40% EtOAc/pentane

Sources & evidence

ORD record
ord-30a2593407e94fff871d3d0bb606845e
Source dataset
uspto-grants-2012_08
Patent number
US08236953B2

Reaction notes

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