tert-Butyl (6-methylpyridin-3-yl)carbamate → tert-butyl N-(6-methylpiperidin-3-yl)carbamate

HRID 2370254Notes

Reaction equation

HRID 2370254 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][C:11]([CH3:14])=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]>CO.[Rh]>[C:1]([O:5][C:6](=[O:15])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 23090429tert-Butyl (6-methylpyridin-3-yl)carbamate

Product 1

HCID 42609251tert-butyl N-(6-methylpiperidin-3-yl)carbamateYield 85%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 887MethanolSolvent

Procedure

A stainless steel autoclave was charged with a solution of the t-butyl-(6-methylpyridin-3-yl)carbamate (6.2 g, 3.12 mmol) in MeOH (100 mL) and treated with 5 wt % Rhodium on alumina (3.06 g, 0.312 mmol). The vessel was evacuated and back-filled with N2 three times. Next, it was evacuated, and then back-filled with H2 to a pressure of 500 psi, and stirred vigorously at room temperature for 2 days. The vessel was depressurized, the mixture was filtered though Celite®, and the filter cake was washed with EtOAc (300 mL). The filtrate was concentrated in vacuo to a tan oil, which was sufficiently pure to use in the subsequent step without further purification (5.4 g, 85% yield, dr=2:1). Data for G-2 (major diastereomer): 1H NMR (500 MHz, CDCl3) δ 5.46 (br s, 1H), 3.71 (br s, 1H), 2.91 (dt, J 12.0, 2.3 Hz, 1H), 2.79 (d, J=10.7 Hz, 1H), 2.57-2.63 (m, 1H), 1.79 (d, J=13.4 Hz, 1H), 1.40-1.61 (m, 3H), 1.42 (s, 9H), 1.10-1.25 (m, 1H); 1.03 (d, J=5.9 Hz, 3H). Data for G-2 (minor diastereomer): 1H NMR (500 MHz, CDCl3) δ 4.38 (br s, 1H), 3.40 (br s, 1H), 3.25 (ddd, J=11.7, 4.2, 2.0 Hz, 1H), 2.50-2.59 (m, 1H), 2.33 (t, J=11.2 Hz, 1H), 1.68 (d, J=9.5 Hz, 1H), 1.40-1.61 (m, 3H), 1.40 (s, 9H), 1.10-1.25 (m, 1H); 1.04 (d, J=6.1 Hz, 3H).

Workup

  1. customThe vessel was evacuated
  2. additionback-filled with N2 three times
  3. customNext, it was evacuated
  4. additionback-filled with H2 to a pressure of 500 psi
  5. filtrationthe mixture was filtered though Celite®
  6. washthe filter cake was washed with EtOAc (300 mL)
  7. concentrationThe filtrate was concentrated in vacuo to a tan oil, which
  8. customto use in the subsequent step without further purification (5.4 g, 85% yield, dr=2:1)

Sources & evidence

ORD record
ord-fe81b61d1e3e4320ae0097f039838d9f
Source dataset
uspto-grants-2014_04
Patent number
US08710076B2

Reaction notes

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