Diisopropylethylamine → 4-[Methyl(tetrahydrofuran-3-yl)amino]piperidine-1-carboxylic acid tert-butyl ester

HRID 1945503Notes

Reaction equation

HRID 1945503 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH3:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:16]1[CH2:20][CH2:19][C:18](=O)[CH2:17]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH3:15])[CH:18]2[CH2:19][CH2:20][O:16][CH2:17]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5293923-OxotetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 15380702tert-Butyl 4-(methylamino)piperidine-1-carboxylate

Product 1

HCID 596055664-[Methyl(tetrahydrofuran-3-yl)amino]piperidine-1-carboxylic acid tert-butyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-(methylamino)piperidine-1-carboxylic acid tert-butyl ester (200 mg, 0.93 mmol), dihydrofuran-3-one (145 μl, 161 mg, 1.87 mmol), 4 Å powdered molecular sieves (550 mg) and DIPEA (323 μl, 241 mg, 1.87 mmol) in DCM (10 mL) was stirred at room temperature for 30 min before the addition of sodium triacetoxyborohydride (396 mg, 1.87 mmol). The reaction mixture was stirred at room temperature for 16 h then diluted with DCM and washed with H2O. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording the title compound as an oil (132 mg, 50%). 1H NMR (CDCl3, 300 MHz): δ 4.33-4.05 (m, 2 H); 4.01-3.91 (m, 1 H); 3.90-3.73 (m, 2 H); 3.68-3.48 (m, 1 H); 3.47-3.23 (m, 1 H); 2.72-2.56 (m, 2 H); 2.21 (s, 3 H); 2.11-1.94 (m, 1 H); 1.93-1.78 (m, 1 H); 1.76-1.63 (m, 2 H); 1.76-1.63 (m, 1 H); 1.54-1.46 (m, 2 H); 1.46 (s, 9 H).

Workup

  1. washwashed with H2O
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-32cc7c8f0ea34edda654e5a25dea306b
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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