Dicyclohexylcarbodiimide → 1-[[3-Chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione

HRID 393002Notes

Reaction equation

HRID 393002 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12].O[N:16]1[C:20](=[O:21])[CH2:19][CH2:18][C:17]1=[O:22].C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12])[C:8]([O:10][N:16]1[C:20](=[O:21])[CH2:19][CH2:18][C:17]1=[O:22])=[O:9]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 212765331,4-Benzenedicarboxylic acid, 2-chloro-, 1-methyl ester

Product 1

HCID 235607681-[[3-Chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedioneYield 112.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A 3-neck 1 L round-bottom flask equipped with a magnetic stirrer, ice cooling bath, thermometer and an argon inlet tube was set up and charged with 2-chloro-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 1; 21.5 g, 0.1 mol) in tetrahydrofuran (250 mL). The solution was cooled to 10° C. under argon and was treated in succession with N-hydroxysuccinimide (12.66 g, 0.11 mol) and 1,3-dicyclohexylcarbodiimide (21.66 g, 0.105 mol). These reagents were washed in with additional tetrahydrofuran (100 mL). A precipitate started to form immediately. The cooling bath was removed and the reaction mixture was stirred at ambient temperature overnight, and then diluted with diethyl ether (400 mL) and stirred for another 30 min. The precipitate was collected by filtration, and the filter cake was washed with diethyl ether (3×50 mL). The dried solids (DCU) weighed 22.2 g (>99% of theory). The combined filtrates were diluted with hexane (100 mL) then were transferred to a 2 L separatory funnel and were washed in turn with cold saturated sodium bicarbonate solution (150 mL) and brine (150 mL). Each aqueous layer was back-extracted in turn with diethyl ether (200 mL), then the combined organic extracts were dried (MgSO4), and evaporated to give crude 1-[[3-chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione (˜35 g) as a colorless solid. This material was used directly in the next step without purification.

Workup

  1. customA 3-neck 1 L round-bottom flask equipped with a magnetic stirrer, ice cooling bath
  2. customthermometer and an argon inlet tube was set up
  3. washThese reagents were washed in with additional tetrahydrofuran (100 mL)
  4. customto form immediately
  5. customThe cooling bath was removed
  6. additiondiluted with diethyl ether (400 mL)
  7. stirringstirred for another 30 min
  8. filtrationThe precipitate was collected by filtration
  9. washthe filter cake was washed with diethyl ether (3×50 mL)
  10. additionThe combined filtrates were diluted with hexane (100 mL)
  11. customthen were transferred to a 2 L separatory funnel
  12. washwere washed in turn with cold saturated sodium bicarbonate solution (150 mL) and brine (150 mL)
  13. extractionEach aqueous layer was back-extracted in turn with diethyl ether (200 mL)
  14. dry with materialthe combined organic extracts were dried (MgSO4)
  15. customevaporated

Sources & evidence

ORD record
ord-07976de11f074b1e8028c255ca51f3b8
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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