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

HRID 12922

Reaction equation

HRID 12922 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(O[CH2:29][C@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])(C1C=CC(C)=CC=1)(=O)=O>CN(C=O)C>[C:38]([O:37][C:35]([N:31]1[CH2:32][CH2:33][CH2:34][CH:30]1[CH2:29][O:17][C:14]1[CH:13]=[CH:12][C:11]([O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:16][CH:15]=1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 3

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

Product 1

HCID 597530242-(4-Benzyloxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 55.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a 15 mL of anhydrous DMF was added NaH (60% dispersion in oil, 338 mg, 8.44 mmol), and the resulting reaction mixture was cooled to 0° C. p-benzyloxy phenol (1.41 g, 7.03 mmol) was added and the reaction mixture was stirred at rt for 45 min. It was then cooled to −5° C., and (R)-Boc-prolinol tosylate (2.5 g, 7.03 mmol) in anhydrous DMF (5 mL) was cooled in a separate ice-bath and added dropwise to the reaction mixture. It was then allowed to warm to rt and stirred at 92° C. for 5 h and at rt overnight. The resulting mixture was poured into 200 mL ice/water and stirred for an hour. The resulting precipitate was filtered, washed with ether, dried over MgSO4, concentrated, recrystallized with ether/hexane to give shiny yellow crystals (1.5 g, 55%).

Workup

  1. customthe resulting reaction mixture
  2. additionwas added
  3. temperatureIt was then cooled to −5° C.
  4. additionadded dropwise to the reaction mixture
  5. temperatureto warm to rt
  6. stirringstirred at 92° C. for 5 h and at rt overnight
  7. stirringstirred for an hour
  8. filtrationThe resulting precipitate was filtered
  9. washwashed with ether
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customrecrystallized with ether/hexane

Sources & evidence

ORD record
ord-188a746988c84b5d953e1fe0403ef6ff
Source dataset
uspto-grants-2010_06
Patent number
US07728032B2

Linked notes

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