Triethylamine → Boc-prolylproline methyl ester

HRID 2370885Notes

Reaction equation

HRID 2370885 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.Cl.[CH3:31][O:32][C:33](=[O:39])[C@@H:34]1[CH2:38][CH2:37][CH2:36][NH:35]1>C(Cl)Cl>[CH3:31][O:32][C:33](=[O:39])[C@@H:34]1[CH2:38][CH2:37][CH2:36][N:35]1[C:10](=[O:12])[C@@H:9]1[CH2:13][CH2:14][CH2:15][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2733200methyl L-prolinate hydrochloride

Product 1

HCID 14236281Boc-prolylproline methyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

METHOD 1 N-tert-butoxycarbonyl L-proline (99.69 g, 0.4631 mol) was dissolved in CH2Cl2 (800 mL). The solution was cooled to 0° C. (icebath) and triethylamine (51.50 g, 0.5089 mol) added. Pivaloyl chloride (61.45 g, 0.5096 mol) was added dropwise, resulting in the precipitation of a white solid. The reaction mixture was stirred for 1 hour at 0° C. before triethylamine (102.99 g, 1.018 mol) was added. Next, L-proline methyl ester hydrochloride (76.87 g, 0.4641 mol) was added in small portions. The icebath was removed and the reaction mixture stirred at room temperature for 17 hours. The volume was increased by addition of CH2Cl2 (2 L) and the solution washed with 30% (w/w) aqueous citric acid (3×1400 mL), saturated NaHCO3 solution (3×1400 mL) and saturated brine (2×1400 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a clear oil (129.14 g, 85%) with spectral characteristics in accordance with literature data.1

Workup

  1. additionadded
  2. customresulting in the precipitation of a white solid
  3. additionwas added
  4. customThe icebath was removed
  5. temperatureThe volume was increased by addition of CH2Cl2 (2 L)
  6. washthe solution washed with 30% (w/w) aqueous citric acid (3×1400 mL), saturated NaHCO3 solution (3×1400 mL) and saturated brine (2×1400 mL)
  7. dry with materialThe solution was dried with anhydrous MgSO4
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-4645b83c97b04a9f84d9634643c9845f
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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