Trifluoroacetic acid → HCID 22498718, compound

HRID 2307286Notes

Reaction equation

HRID 2307286 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1C(OC(C)(C)C)=O)[OH:7].FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([CH:8]1[CH2:12][CH2:11][CH2:10][NH:9]1)[OH:7]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 22498771HCID 22498771, compound

Product 1

HCID 22498718HCID 22498718, compoundYield 7.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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, 2-furaldehyde (2.9 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 (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; 5/1) to afford 4.97 g of 2-furyl(N-Boc-pyrrolidin-2-yl)methanol as a mixture of diastereomers. The resulting 2-furyl(N-Boc-pyrrolidin-2-yl)methanol (4.43 g) is dissolved in dichloromethane (200 mL) and trifluoroacetic acid (30 mL) is added. The mixture is poured into a 1 M solution of sodium hydroxide. The organic layer is separated and washed with saturated aq. sodium bicarbonate (2×100 mL). The aqueous layers are extracted with dichloromethane (4×50 mL) and the combined organic layers are concentrated. The crude product is purified by column chromatography (CH2Cl2/methanol/NH4OH, 95/5/1; 90/10/1). The resulting oil is distilled in a Kugelrohr apparatus (0.175-200° C., 0.2 Torr) to afford 0.20 g of the title compound as a mixture of diastereomers. Physical characteristics. MS (ESI+) m/z 168 (M+H)+.

Workup

  1. additionas a mixture of diastereomers
  2. customThe organic layer is separated
  3. washwashed with saturated aq. sodium bicarbonate (2×100 mL)
  4. extractionThe aqueous layers are extracted with dichloromethane (4×50 mL)
  5. concentrationthe combined organic layers are concentrated
  6. customThe crude product is purified by column chromatography (CH2Cl2/methanol/NH4OH, 95/5/1; 90/10/1)
  7. distillationThe resulting oil is distilled in a Kugelrohr apparatus (0.175-200° C., 0.2 Torr)

Sources & evidence

ORD record
ord-0e6488f397e14c5598f4a0f579ee2995
Source dataset
uspto-grants-2004_12
Patent number
US06831081B2

Reaction notes

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