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

HRID 1246880Notes

Reaction equation

HRID 1246880 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-ce73ab6dfb324008b708e6660935cffd
Source dataset
uspto-grants-2006_10
Patent number
US07129228B2

Reaction notes

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