Monobenzone → (R)-2-(4-Benzyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1909810Notes

Reaction equation

HRID 1909810 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@@H:26]1[CH2:30]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@@H:26]1[CH2:30][O:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 7638MonobenzoneHCID 24758Sodium hydrideHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 68999348(R)-2-(4-Benzyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 86.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To p-benzyloxyphenol (7.05 g, 35.2 mmol) was added to a solution of NaH (60% dispersion in oil, 1.70 g, 42.2 mmol) in anhy. DMF (70 mL) at 0° C. The mixture was stirred at ambient temperature for 30 min, then cooled to −10° C. and (R)-2-(Toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (12.5 g, 35.2 mmol) in anhy.DMF (20 mL) was added dropwise over 5 min. The mixture was stirred at 92° C. for 5 h and then ambient temperature overnight. The reaction mixture was poured into ice water and stirred for one h. The subsequent mixture was filtered and the organic portion was extracted into ether. The portion was dried over anhy. MgSO4, and concentrated to afford the product (11.7 g, 86%).

Workup

  1. customat 0° C
  2. temperaturecooled to −10° C.
  3. stirringThe mixture was stirred at 92° C. for 5 h
  4. customambient temperature overnight
  5. stirringstirred for one h
  6. filtrationThe subsequent mixture was filtered
  7. extractionthe organic portion was extracted into ether
  8. customThe portion was dried over anhy
  9. concentrationMgSO4, and concentrated

Sources & evidence

ORD record
ord-14f1d5b0d053419eb4497e7aac691553
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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