3-Fluorophenol → 4-(3-Fluoro-phenoxymethyl)-pyrroline-1,2-dicarboxylic acid di-tert-butyl ester

HRID 1442973Notes

Reaction equation

HRID 1442973 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH2:13][OH:14])[CH2:10][CH:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:41][C:42]1[CH:43]=[C:44](O)[CH:45]=[CH:46][CH:47]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH2:13][O:14][C:46]2[CH:45]=[CH:44][CH:43]=[C:42]([F:41])[CH:47]=2)[CH:10]=[C:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 97433-FluorophenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 189679154-Hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester

Product 1

HCID 669401524-(3-Fluoro-phenoxymethyl)-pyrroline-1,2-dicarboxylic acid di-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester (Preparation 42, 500 mg, 1.66 mmol), triphenylphosphine (653 mg, 2.49 mmol) and 3-fluorophenol (0.23 ml, 2.49 mmol) in tetrahydrofuran (30 ml) at 0° C. under a nitrogen atmosphere was added diisopropylazodicarboxylate (0.49 ml, 2.49 mmol) dropwise over 5 minutes and stirred to room temperature over 72 hours. Solvent was removed under reduced pressure and the residue purified by chromatography on silica gel, eluting with 10-15% ethyl acetate/heptane to give the title compound as a mixture of diastereomers (˜5:1 2S,4S:2S,4R) as a colourless oil (370 mg, 51%)

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe residue purified by chromatography on silica gel
  3. washeluting with 10-15% ethyl acetate/heptane

Sources & evidence

ORD record
ord-ddae5aca3cf844219d01a15385333605
Source dataset
uspto-grants-2010_02
Patent number
US07659305B2

Reaction notes

Loading…