Phthalimide → 1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-phenyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1295357Notes

Reaction equation

HRID 1295357 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[C@@:10]([CH2:14]O)([CH2:11]2)[C@@H:9]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:41]1(=[O:51])[NH:45][C:44](=[O:46])[C:43]2=[CH:47][CH:48]=[CH:49][CH:50]=[C:42]12.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([CH2:14][N:45]3[C:41](=[O:51])[C:42]4[C:43](=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:44]3=[O:46])([CH2:11]2)[CH:9]1[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 69336539(1S,2S,5S)-1-hydroxymethyl-2-phenyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

Product 1

HCID 693429221-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-phenyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To racemic Intermediate 19, one enantiomer being (1S,2S,5S)-1-hydroxymethyl-2-phenyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (0.40 g, 1.4 mmol), was added anhydrous THF (5 mL), triphenylphosphine (0.43 g, 1.6 mmol), phthalimide (0.30 g, 2.1 mmol), and diethylazodicarboxylate (0.22 mL, 1.7 mmol). The reaction was allowed to stir at room temperature for 16 hours. The solvent was removed at reduced pressure and the residue partitioned between saturated sodium bicarbonate solution and methylene chloride, the organics were washed with brine, dried over sodium sulfate, filtered, and concentrated to an oil. The material was purified by chromatography on silica by elution with a gradient of 5 to 20% EtOAc/Hexanes to give the title compound as an white solid (0.56 g, 97% yield).

Workup

  1. customThe solvent was removed at reduced pressure
  2. customthe residue partitioned between saturated sodium bicarbonate solution and methylene chloride
  3. washthe organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customThe material was purified by chromatography on silica by elution with a gradient of 5 to 20% EtOAc/Hexanes

Sources & evidence

ORD record
ord-ec889b950005468eadf3e601f7fd2a82
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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