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

HRID 2103733Notes

Reaction equation

HRID 2103733 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[CH2:15]([NH:22][CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7504BenzylamineHCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 15380687tert-Butyl 4-(benzylamino)piperidine-1-carboxylateYield 92.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-piperidone (10.0 g, 50.2 mmol), benzylamine (5.4 g, 50.2 mmol), and acetic acid (3.01 g, 50.2 mmol) in 200 mL of dry dichloromethane was added sodium triacetoxyborohydride (21.2 g, 100 mmol) under nitrogen. The mixture was stirred for three days, and then aqueous 1 N NaOH (200 mL) solution was added. After 1 h of stirring, the layers were separated, and the aqueous layer was extracted twice with dichloromethane (100 mL). The organic extracts were combined, washed twice with 1 N NaOH (100 mL), dried (Na2SO4), and concentrated to give 13.46 g of 4-benzylamino-1-(tert-butoxycarbonyl)piperidine as a cream-colored waxy solid. MS (ES), m/z 291 (MH+). 300 MHz 1H NMR (CDCl3) δ1.22-1.39 (br q, 2H), 1.45 (s, 9H), 1.86 (br d, J=11.3 Hz, 2H), 2.60-2.93 (m, 4H), 3.82 (s, 2H), 3.85-4.20 (br m, 2H), 7.19-7.37 (m, 5H).

Workup

  1. stirringAfter 1 h of stirring
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane (100 mL)
  4. washwashed twice with 1 N NaOH (100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bd86b28081f64791a9fe9dca7f074130
Source dataset
uspto-grants-2009_08
Patent number
US07576105B2

Reaction notes

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