Phenol → 1-(3-Fluoro-4-methoxyphenyl)-4-(phenoxymethyl)pyrrolidin-2-one

HRID 1993376Notes

Reaction equation

HRID 1993376 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:10]2[CH2:14][CH:13]([CH2:15][OH:16])[CH2:12][C:11]2=[O:17])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:18]1(O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:10]2[CH2:14][CH:13]([CH2:15][O:16][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:12][C:11]2=[O:17])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 642108121-(3-Fluoro-4-methoxyphenyl)-4-(hydroxymethyl)pyrrolidin-2-one

Product 1

HCID 684201161-(3-Fluoro-4-methoxyphenyl)-4-(phenoxymethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-fluoro-4-methoxyphenyl)-4-(hydroxymethyl)pyrrolidin-2-one (Step 2, 1.0 g, 4.18 mmol), phenol (0.786 g, 8.36 mmol) and PPh3 (2.41 g, 9.2 mmol) in 50 mL of CH2Cl2 at 0° C. was added DIAD (1.65 mL, 9.2 mmol) slowly via a syringe. The reaction was warmed to RT and stirred overnight. The mixture was concentrated in vacuo and the residue was purified by chromatography (hexanes to 50% EtOAc/hexanes) to give the title compound as a white solid. MS (ESI pos. ion) m/z: 316.2 (M+H). Calc'd Exact Mass for C18H18FNO3: 315.34.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was purified by chromatography (hexanes to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b6deadc0ccc347c48ea2d3308b03d1f2
Source dataset
uspto-grants-2010_01
Patent number
US07652009B2

Reaction notes

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