Benzaldehyde → HCID 22498732, compound

HRID 1814883Notes

Reaction equation

HRID 1814883 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.[CH:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(OCC)C>[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH:12]1[CH:18]([OH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 643455N-Boc-pyrrolidineHCID 178418400CID 53628100

Product 1

HCID 22498732HCID 22498732, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

N-Boc-pyrrolidine (5.0 g) was dissolved in diethyl ether (60 mL) and the solution was cooled to −78° C. N,N,N′,N″-Tetramethylethylenediamine (TMEDA) (4.4 mL) was 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, benzaldehyde (3.6 mL) was added and the mixture was stirred at −70° C. for an additional 30 min. The reaction mixture was allowed to warm to room temperature and was then quenched with water and poured into EtOAc (200 mL). The separated organic layer was washed with saturated aq. ammonium chloride (3×50 mL) followed by brine (50 mL), dried (MgSO4), and concentrated. The crude product was purified by column chromatography (heptane/EtOAc, 8/1; 6/1) to afford 6.3 g of N-Boc-2-(hydroxy(phenyl)methyl)-pyrrolidine as a mixture of diastereomers. The resulting N-Boc-2-(hydroxy(phenyl)methyl)pyrrolidine (5.6 g) was dissolved in dichloromethane (500 mL) and trifluoroacetic acid (60 mL) was added. The mixture was concentrated, dissolved in dichloromethane (200 mL), and washed with saturated aq. sodium bicarbonate (3×100 mL). The aqueous layers were extracted with dichloromethane (4×50 mL) and the combined organic layers were concentrated. The crude product was distilled in a Kugelrohr apparatus (150-175° C., 0.2 Torr) to afford 2.47 g of the title compound as a mixture of diastereomers. Physical characteristics. MS (ESI+) m/z 178 (M+H)+.

Workup

  1. temperaturemaintaining the temperature below −60° C
  2. temperatureto warm to room temperature
  3. customwas then quenched with water
  4. additionpoured into EtOAc (200 mL)
  5. washThe separated organic layer was washed with saturated aq. ammonium chloride (3×50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (heptane/EtOAc, 8/1; 6/1)

Sources & evidence

ORD record
ord-6726f4dd5acd4758a67873f7e4884663
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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