1,1'-Carbonyldiimidazole → HCID 57692649, compound

HRID 2081124Notes

Reaction equation

HRID 2081124 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, compound

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 (500 mg, 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. The amine, 4-chloroisoindoline hydrochloride (0.89 g, 4.7 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 the ester product, (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-b2d42838241d4e94a033f1825e780a29
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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