1-N-Cbz-3-pyrrolidinone → Benzyl 3-{3-[(tert-butoxycarbonyl)amino]pyridin-4-yl}-3-hydroxypyrrolidine-1-carboxylate

HRID 557897

Reaction equation

HRID 557897 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:2]=1.C([Li])(C)(C)C.[O:20]=[C:21]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22]1>C1COCC1.CCCCC>[C:10]([O:9][C:8]([NH:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][C:4]=1[C:21]1([OH:20])[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22]1)=[O:14])([CH3:11])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 5612031-N-Cbz-3-pyrrolidinoneHCID 109323213-(Boc-amino)pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 66661951Benzyl 3-{3-[(tert-butoxycarbonyl)amino]pyridin-4-yl}-3-hydroxypyrrolidine-1-carboxylateYield 25.5%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a flame-dried round bottomed flask with thermometer side-arm, equipped with a stir bar, was added tert-butyl pyridin-3-ylcarbamate (1.104 g, 0.005684 mol) in 75 mL THF under inert atmosphere. The solution was cooled to −78° C. and then 1.7 M of tert-butyllithium in pentane (7.4 mL) was added dropwise. The resulting solution was stirred for 2 h at −78° C., followed by the addition of benzyl 3-oxopyrrolidine-1-carboxylate (1.038 g, 0.004736 mol) in 75 mL THF. The reaction was allowed to warm to rt and stirred for 5 hrs. The reaction mixture was quenched with saturated ammonium chloride, diluted with water and extracted with ethyl acetate. The combined organic phases were treated with brine and then magnesium sulfate, filtered, and concentrated. The crude product was purified by combiflash using 50-80% ethyl acetate/hexane to recover the starting material (0.9 g) and then 100% ethyl acetate to obtain the product (0.5 g). The product was verified by LCMS and NMR data.

Workup

  1. customTo a flame-dried round bottomed flask with thermometer side-arm, equipped with a stir bar
  2. temperatureto warm to rt
  3. stirringstirred for 5 hrs
  4. customThe reaction mixture was quenched with saturated ammonium chloride
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. additionThe combined organic phases were treated with brine
  8. filtrationmagnesium sulfate, filtered
  9. concentrationconcentrated
  10. customThe crude product was purified by combiflash
  11. customto recover the starting material (0.9 g)

Sources & evidence

ORD record
ord-7010c878a10149219fa1f776359b7be6
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Linked notes

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