2-Pyridinecarboxaldehyde → HCID 22605709, compound

HRID 2307283Notes

Reaction equation

HRID 2307283 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([Li])(CC)C.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]=[O:25]>C(OCC)C>[OH:25][CH:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=1)[CH:12]1[CH2:11][CH2:10][CH2:9][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 142732-PyridinecarboxaldehydeHCID 643455N-Boc-pyrrolidineHCID 178418400CID 53628100

Product 1

HCID 22605709HCID 22605709, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

N-Boc-pyrrolidine (5.0 g) is dissolved in diethyl ether (60 mL) and the solution is cooled to −78° C. N,N,N′,N′-Tetramethylenediamine (TMEDA) (4.4 mL) is added to the mixture followed by sec-butyl lithium (27.0 mL, 1.3 M in cyclohexane) maintaining the temperature below −60° C. After 2 h, 2-pyridine carboxaldehyde (3.3 mL) is added and the mixture is stirred at −70° C. for an additional 30 min. The reaction mixture is allowed to warm to room temperature and is then quenched with water (25 mL) and poured into EtOAc (250 mL). The separated organic layer is washed with water (2×50 mL) followed by brine (50 mL), dried (Na2SO4), and concentrated. The crude product is purified by column chromatography (heptane/EtOAc, 4/1; 2/1, 1/1) to afford 4.79 g of tert-butyl 2-(hydroxy(pyridin-2-yl)methyl)pyrrolidine-1-carboxylate as a mixture of diastereomers. The resulting alcohol is dissolved in dichloromethane (10 mL) and trifluoroacetic acid (80 mL) is added with ice bathe cooling. After 1 h, the reaction mixture is concentrated and added to 1 N sodium hydroxide solution (200 mL). The mixture is extracted with CH2Cl2 (3×100 mL). The combined organic layers are dried (Na2SO4) and concentrated. The resulting oil is distilled in a Kugelrohr apparatus (175-200° C., 0.2 Torr) to afford 2.04 g of the title compound as a mixture of diastereomers. Physical characteristics. 1H NMR (400 MHz, DMSO-d6) δ 8.47, 7.76, 7.46, 7.24, 5.27, 4.50, 4.34, 3.32, 3.22, 2.83, 2.68, 1.62-1.36; MS (ESI+) m/z 179 (M+H)+.

Workup

  1. temperaturemaintaining the temperature below −60° C
  2. temperatureto warm to room temperature
  3. customis then quenched with water (25 mL)
  4. additionpoured into EtOAc (250 mL)
  5. washThe separated organic layer is washed with water (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product is purified by column chromatography (heptane/EtOAc, 4/1; 2/1, 1/1)

Sources & evidence

ORD record
ord-110c6f4021484bd58364f542b1ee5acf
Source dataset
uspto-grants-2004_12
Patent number
US06831081B2

Reaction notes

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