1,1'-Carbonyldiimidazole → HCID 57692649, compound

HRID 2081133Notes

Reaction equation

HRID 2081133 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.C1N=CN([C:23]([N:25]2[CH:29]=N[CH:27]=[CH:26]2)=[O:24])C=1.Cl.[Cl:31][C:32]1[CH:40]=CC=[C:37]2[C:33]=1CN[CH2:36]2.CCN(C(C)C)C(C)C>C1COCC1.CCOC(C)=O>[Cl:31][C:32]1[CH:33]=[CH:37][CH:36]=[C:27]2[C:40]=1[CH2:29][N:25]([C:23]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)=[O:24])[CH2:26]2

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 426096444-Chloro-2,3-dihydro-1H-isoindole--hydrogen chloride (1/1)

Product 1

HCID 57692649HCID 57692649, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (0.50 g, 2.04 mmol) in dry THF (6 mL) was added CDI (430 mg, 2.65 mmol) in one portion and the mixture was stirred at rt for 6 h. 4-chloroisoindoline hydrochloride (0.89 g, 4.69 mmol) was then added in portions, followed by slow addition of DIEA (1.07 mL, 6.12 mmol). The reaction was stirred at rt for overnight. The reaction was diluted with 120 mL EtOAc, washed with 1N HCl (2×50 mL), water and brine (50 mL each), and dried over Na2SO4 and concentrated down to a thick brownish oil. The crude was purified by silica chromatography (eluent=hexanes/EtOAc 2:1), giving (2S,4R)-1-tert-butyl 2-methyl 4-(4-chloroisoindoline-2-carbonyloxy)pyrrolidine-1,2-dicarboxylate as a light pinkish foamy solid (0.79 g, 91% yield).

Workup

  1. stirringThe reaction was stirred at rt for overnight
  2. washwashed with 1N HCl (2×50 mL), water and brine (50 mL each)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated down to a thick brownish oil
  5. customThe crude was purified by silica chromatography (eluent=hexanes/EtOAc 2:1)

Sources & evidence

ORD record
ord-72e39bfde04d4d1492f54bc4e4783e7c
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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