Allyl bromide → benzyl rel-(3R,4R)-3-(allyloxy)-4-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylate

HRID 564397Notes

Reaction equation

HRID 564397 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:13]([OH:14])[CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:27](Br)[CH:28]=[CH2:29]>C1COCC1>[CH2:29]([O:14][C@H:13]1[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:10][N:11]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:12]1)[CH:28]=[CH2:27]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 59640637benzyl (3R,4R)-3-((tert-butoxycarbonyl)amino)-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 59556149benzyl rel-(3R,4R)-3-(allyloxy)-4-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylateYield 72.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzyl rel-(3R,4R)-3-[(tert-butoxycarbonyl)amino]-4-hydroxypyrrolidine-1-carboxylate (1 g, 2.97 mmol) in dry THF (10 mL) at 0° C. was added NaH (475 mg, 11.88 mmol). The reaction mixture was stirred at 0° C. for 1 h. Allyl bromide (1.08 g, 8.92 mmol) was added to the reaction mixture dropwise. The reaction mixture was stirred at 0° C. for 2 h and room temperature for 1 h. The reaction was quenched by adding MeOH (5 mL) and was concentrated under reduced pressure to remove most of the solvent. Then water (15 mL) was added to the reaction mixture. EtOAc (15 mL×3) was added to extract the product. The organic phases were combined, dried over MgSO4, filtered, concentrated and subjected to column chromatography (EtOAc:hexanes, 1:3 to 1:1) as the eluent to give benzyl rel-(3R,4R)-3-(allyloxy)-4-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylate (806.2 mg, 72%).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 2 h and room temperature for 1 h
  2. customThe reaction was quenched
  3. additionby adding MeOH (5 mL)
  4. concentrationwas concentrated under reduced pressure
  5. customto remove most of the solvent
  6. additionThen water (15 mL) was added to the reaction mixture
  7. additionEtOAc (15 mL×3) was added
  8. extractionto extract the product
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4bc8578c95ce4ba0ad1f18a93bc9f10f
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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