Sodium Iodide → N-Cbz-4-hydroxyproline benzyl ester

HRID 340813Notes

Reaction equation

HRID 340813 reaction equation
[C:1]([N:11]1[CH2:18][CH:17]([OH:19])[CH2:16][C@H:12]1[C:13]([OH:15])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C([O-])([O-])=O.[K+].[K+].[Na+].[I-].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(OCC)(=O)C.CN(C=O)C>[CH2:28]([O:14][C:13](=[O:15])[C@@H:12]1[CH2:16][CH:17]([OH:19])[CH2:18][N:11]1[C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 12731799(2S)-1-((benzyloxy)carbonyl)-4-hydroxypyrrolidine-2-carboxylic acid

Product 1

HCID 57008512N-Cbz-4-hydroxyproline benzyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Cbz-4-hydroxyproline (40.00 g, 150.8 mmol) 8 was dissolved into 110 mL DMF. To this mixture was added 45.85 g of K2CO3 (2.2 eq; 331.7 mmol) and 2.30 g of NaI (0.1 eq). The reaction flask was purged with argon and 55.4 mL of benzylbromide (3 eq; 452 mmol) was added dropwise. This mixture was then stirred over night at room temperature. The reaction was then diluted with 300 mL ethyl acetate and washed with water (8×200 mL) to remove DMF, followed by washing with 100 mL brine. The organic layer was dried over Na2SO4 and concentrated to a yellow oil. The oil was then washed several times with 100 mL hexanes to remove any remaining benzyl bromide and then separated by silica gel in hexanes:ethyl acetate, 3:2, isolating N-Cbz-4-hydroxyproline benzyl ester at Rf=0.25 in nearly quantitative yield. 1H and 13C NMR spectra were in agreement with 1H and 13C NMR spectra previously reported (Robinson et al., 1998).

Workup

  1. additionwas added dropwise
  2. washwashed with water (8×200 mL)
  3. customto remove DMF
  4. washby washing with 100 mL brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated to a yellow oil
  7. washThe oil was then washed several times with 100 mL hexanes
  8. customto remove any remaining benzyl bromide
  9. customseparated by silica gel in hexanes

Sources & evidence

ORD record
ord-2459ecbeefc8459ab7e11610caa803e7
Source dataset
uspto-grants-2014_11
Patent number
US08895607B2

Reaction notes

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