2-Fluoropyridine → HCID 67019304, compound

HRID 1497034Notes

Reaction equation

HRID 1497034 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:9]1>CCO>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:18])([CH3:17])[CH3:19])[CH2:9]1

Participants

4

Reactant 2

HCID 97462-FluoropyridineHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamate

Product 1

HCID 67019304HCID 67019304, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-fluoropyridine (58.3 mg, 0.600 mmol), tert-butyl pyrrolidin-3-ylcarbamate (55.9 mg, 0.300 mmol), and TEA (84.0 μL, 0.600 mmol) in EtOH (1 mL) was heated at 120° C. for 30 min. The reaction was concentrated and the crude was purified by flash chromatography (12 g silica gel) using hexanes/EtOAc (0-50% over 10 min, flow rate 30 mL/min) to give Intermediate 48A (15 mg, 0.057 mmol, 19% yield) as a white solid. LCMS=264.3 [M+1], RT=1.11 min (Method H). 1H NMR (400 MHz, chloroform-d) δ ppm 8.15 (1H, dd, J=5.05, 1.01 Hz), 7.44 (1H, ddd, J=8.59, 6.95, 1.89 Hz), 6.55 (1H, dd, J=6.44, 5.18 Hz), 6.35 (1H, d, J=8.34 Hz), 4.74 (1H, br. s.), 4.35 (1H, br. s.), 3.71 (1H, dd, J=10.61, 6.06 Hz), 3.46-3.64 (2H, m), 3.34 (1H, dd, J=10.61, 4.04 Hz), 2.27 (1H, td, J=13.20, 7.45 Hz), 1.96 (1H, td, J=12.51, 5.56 Hz), 1.45 (9H, s).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe crude was purified by flash chromatography (12 g silica gel)
  3. customhexanes/EtOAc (0-50% over 10 min, flow rate 30 mL/min)

Sources & evidence

ORD record
ord-2a555c6e55f24b4d9c48de41da40877c
Source dataset
uspto-grants-2015_12
Patent number
US09199946B2

Reaction notes

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