Dimethyl Sulfoxide → 1-t-Butoxycarbonyl-4-oxo-N-t-butyl-L-prolinamide

HRID 1780272Notes

Reaction equation

HRID 1780272 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([O:15][C:16]([N:18]1[CH2:29][C@H:28]([OH:30])[CH2:27][C@H:19]1[C:20]([NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[CH2:29][C:28](=[O:30])[CH2:27][C@H:19]1[C:20]([NH:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[O:17])([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 10334194Boc-Hyp-NH-tBu

Product 1

HCID 228727081-t-Butoxycarbonyl-4-oxo-N-t-butyl-L-prolinamideYield 73.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1.21 g (15.51 mmol) of dimethyl sulfoxide in 5 ml of methylene chloride was added to a solution of 0.98 g (7.72 mmol) of oxalyl chloride in 20 ml of methylene chloride at -50° to -60° C. After 5 minutes, a solution of 2.0 g (7.00 mmol) of (4R)-1-t-butoxycarbonyl-4-hydroxy-N-t-butyl-L-prolinamide (prepared as described in Preparation 5) in 40 ml of methylene chloride was added to the resulting mixture. The mixture was stirred for 15 minutes, after which 3.5 g (35.00 mmol) of triethylamine were added, and the mixture was stirred for a further 5 minutes. The temperature of the reaction mixture was then allowed to rise to room temperature, and the mixture was stirred for a further 1 hour. At the end of this time, the reaction mixture was poured into ice-water and extracted with methylene chloride. The organic extract was washed with a 10% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was recrystallized from a mixture of methylene chloride and diethyl ether, to give 1.47 g of the title compound as colorless crystals, melting at 147°-149° C.

Workup

  1. stirringthe mixture was stirred for a further 5 minutes
  2. customto rise to room temperature
  3. stirringthe mixture was stirred for a further 1 hour
  4. extractionextracted with methylene chloride
  5. extractionThe organic extract
  6. washwas washed with a 10% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  7. dry with materialafter which it was dried over anhydrous sodium sulfate
  8. customThe solvent was then removed by distillation under reduced pressure
  9. customthe resulting residue was recrystallized from a mixture of methylene chloride and diethyl ether

Sources & evidence

ORD record
ord-a48a33cd23134667887f47cb6002ff43
Source dataset
uspto-grants-1997_05
Patent number
US05629406

Reaction notes

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