Benzaldehyde → HCID 22498732, compound

HRID 2307281Notes

Reaction equation

HRID 2307281 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].CN(C)CCN(C)C.C([Li])(CC)C.[CH:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(OCC)C>[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH:12]1[CH:26]([OH:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 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) is dissolved in diethyl ether (60 mL) and the solution is cooled to −78° C. N,N,N′,N′-Tetramethylethylenediamine (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, benzaldehyde (3.6 mL) is added and the mixture is stirred at −70° C. for an additional 30 mL The reaction mixture is allowed to warm to room temperature and is then quenched with water and poured into EtOAc (200 mL). The separated organic layer is washed with saturated aq. ammonium chloride (3×50 mL) followed by brine (50 mL), dried (MgSO4), and concentrated. The crude product is 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 diasteromers. The resulting N-Boc-2-(hydroxy(phenyl)-methyl)pyrrolidine (5.6 g) is dissolved in dichloromethane (500 mL) and trifluoroacetic acid (60 mL) is added. The mixture is concentrated, dissolved in dichloromethane (200 mL), and washed with saturated aq. sodium bicarbonate (3×100 DL). The aqueous layers are extracted with dichloromethane (4×50 mL) and the combined organic layers are concentrated. The crude product is distilled in a Kugelrohr apparatus (150-175° C., 0.2 Torr) to afford 2.47 g of the title compound as a mixture of diasteromers. Physical characteristics. MS (ESI+) m/z 178 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-c0be67b0e2414571bc2954a907bc5b8f
Source dataset
uspto-grants-2004_12
Patent number
US06831081B2

Reaction notes

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