3-Methoxyphenol → (2R,4R)-4-(3-Methoxy-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 732368Notes

Reaction equation

HRID 732368 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[CH2:9][C@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[CH3:18][O:19][C:20]1[CH:21]=[C:22](O)[CH:23]=[CH:24][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)C)=O)=O)(C)C>C1COCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C@H:5]1[CH2:9][C@@H:8]([O:10][C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([O:19][CH3:18])[CH:25]=2)[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

7

Reactant 4

HCID 90073-MethoxyphenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 69512011-tert-Butyl 2-methyl (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 68818220(2R,4R)-4-(3-Methoxy-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 34.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cold solution of (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.15 g, 4.69 mmol) and 3-methoxyphenol (0.56 mL, 5.158 mmol) in THF (10 mL) is added triphenylphosphine (1.84 g, 7.03 mmol) followed by the dropwise addition of diisopropyl-azodicarboxylate (1.40 mL, 7.03 mmol). Warm to room temperature and stir for 18 h. Dilute the reaction with ethyl acetate and wash with 1 N HCl, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry (magnesium sulfate) and purify (silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures) to give the title compound (0.57 g, 34%).

Workup

  1. additionDilute
  2. washwash with 1 N HCl, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. custompurify
  5. wash(silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures)

Sources & evidence

ORD record
ord-f1b3896a65d5445ca72cc87a70a9928d
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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