Aniline → N-(1-Boc-piperidin-3-ylmethyl)aniline

HRID 1839179Notes

Reaction equation

HRID 1839179 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH:14]=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH3-]C#N.[Na+]>CO.COC(OC)OC>[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 6115AnilineHCID 5003444Sodium cyanoborohydrideHCID 99644481-Boc-piperidine-3-carboxaldehyde

Product 1

HCID 12972131N-(1-Boc-piperidin-3-ylmethyl)anilineYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 9005Trimethyl orthoformateSolvent

Procedure

To a solution of N-Boc-piperidin-3-yl-formaldehyde 3 (5.20 g, 24.4 mmol) in 50 mL of dry methanol and 50 mL of trimethylorthoformate was added aniline (2.50 g, 1.1 eq.), and the mixture was stirred at room temperature for 30 minutes. NaBH3CN (95%, 1.84 g, 1.1 eq.) was introduced in one portion, and the mixture was stirred at room temperature overnight. The mixture was quenched with 30 ML of aqueous potassium carbonate (sat.), then extracted with ethyl acetate (3×100 mL). The extracts were combined and washed with aqueous NaHCO3 (sat., 2×50 mL), brine (50 mL), and dried over anhydrous sodium sulfate. After the solvent was removed, the remaining oily residue was purified by a flash column chromatography (silica gel, hexane:ethyl acetate (1:1) to afford N-(1-Boc-piperidin-3-ylmethyl)-aniline 4 as white solid (5.60 g, 79%). IR (film, cm−1) 3520, 3263, 3004, 2976, 2932, 2854, 1688, 1589, 1521, 1482, 1422, 1365, 1267, 1243, 1175, 1150, 794, 709; 1H NMR (CDCl3, ppm) 7.20 (t, 2H, J=7.8 Hz), 6.72 (t, 1H, J=6.8 Hz), 6.63 (d, 2H, J=8.3 Hz), 4.00-3.78 (m, 3H), 3.07-2.70 (m, 4H), 2.00-1.20 (m, 5H), 1.48 (s, overlap, 9H).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe mixture was quenched with 30 ML of aqueous potassium carbonate (sat.)
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washwashed with aqueous NaHCO3 (sat., 2×50 mL), brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customAfter the solvent was removed
  7. customthe remaining oily residue was purified by a flash column chromatography (silica gel, hexane:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-bef11522c07c42faa8fada7bbac6017b
Source dataset
uspto-grants-2004_01
Patent number
US06677332B1

Reaction notes

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