Diisopropylethylamine → 4-[Methyl(tetrahydrofuran-3-yl)amino]piperidine-1-carboxylic acid tert-butyl ester
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
Reactant 4
Product 1
Reagents, catalysts & solvents 1
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, 2H); 4.01-3.91 (m, 1H); 3.90-3.73 (m, 2H); 3.68-3.48 (m, 1H); 3.47-3.23 (m, 1H); 2.72-2.56 (m, 2H); 2.21 (s, 3H); 2.11-1.94 (m, 1H); 1.93-1.78 (m, 1H); 1.76-1.63 (m, 2H); 1.76-1.63 (m, 1H); 1.54-1.46 (m, 2H); 1.46 (s, 9H).
Workup
- washwashed with H2O
- dry with materialThe organic phase was dried (Na2SO4)
- concentrationconcentrated in vacuo
- customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)
Sources & evidence
- ORD record
- ord-06ba144d728040798db908682e94d2bd
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08173650B2
Reaction notes
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