Triphenylphosphine → N-Boc-pyrrolidine

HRID 1280110Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10](O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.COC(=O)/C=C/C1C=CC(O)=CC=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-hydroxycinnamic acid (0.407 g, 2.48 mmol) in EtOAc, a solution of diazomethane in Et2O was added until the yellow color persisted. Excess diazomethane was quenched by the addition of AcOH and the reaction mixture was evaporated to dryness. The residue was dissolved in EtOAc and washed with 10% aqueous HCl, saturated NaHCO3 and brine. The organic layer was dried over anhydrous MgSO4 and evaporated to dryness. The residue was purified by flash column chromatography, using a gradient from 10%-20% EtOAc in hexane, to give E-3-(4-hydroxyphenyl)acrylic acid methyl ester as a white solid (0.362 g). To a solution of (R)-3-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.215 g, 1.15 mmol) in THF at 0° C., triphenylphosphine (0.316 g, 1.21 mmol), diisopropyl azodicarboxylate (236 μL, 1.21 mmol) and E-3-(4-hydroxy-phenyl)-acrylic acid methyl ester (0.215 g, 1.21 mmol) were added. The reaction mixture was stirred for 2 h at 0° C., followed by 4 h at room temperature and then the solvent was evaporated in vacuo. The residue was purified by flash column chromatography, using 20%-30% EtOAc in hexane, to give crude (S)-3-[4-(E)-2-methoxycarbonylvinyl)phenoxy]pyrrolidine-1-carboxylic acid tert-butyl ester as a yellow solid.

Workup

waitfollowed by 4 h at room temperature
customthe solvent was evaporated in vacuo
customThe residue was purified by flash column chromatography

Sources & evidence

ORD record: ord-e0748e1350084c4bbc3931e651432d32
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06448281B1

Reaction notes

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