1-Chloro-4-(chloromethyl)benzene → HCID 67269259, compound

HRID 749922Notes

Reaction equation

HRID 749922 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]([O:13][C:14]([N:16]1[CH2:20][CH2:19][C:18](=[O:21])[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Cl)=[CH:25][CH:24]=1.C([O-])(O)=O.[Na+]>C1COCC1>[C:9]([O:13][C:14]([N:16]1[CH2:17][C:18](=[O:21])[CH:19]([CH2:27][C:26]2[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=2)[CH2:20]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamide

Product 1

HCID 67269259HCID 67269259, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
25 °C

Procedure

To a solution of LDA (1.80 M in THF, 20 mmol) in THF (100 mL) at −78° C., was added a solution of 3-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (10 mmol) in THF (10 mL) dropwise. After 20 min, a solution of 4-chlorobenzyl chloride (15 mmol) in THF (10 mL) was added. Then the mixture was warmed to 25° C. and stirred for 16 h. Satd. aq. NaHCO3 (100 mL) was added, and the organic layer was separated and concentrated to give 3-(4-chloro-benzyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester. This residue (1/8 portion, approx. 1.25 mmol) was diluted with EtOH (10 mL) and treated with benzyl hydrazine hydrogen chloride (1.5 mmol) and K2CO3 (5 mmol). The mixture was stirred at 25° C. for 16 h. Concentration and purification by flash chromatography (EtOAc/CH2Cl2) provided 2-benzyl-3-(4-chloro-phenyl)-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester. A solution of the ester and TFA (2 mL) in CH2Cl2 (10 mL) was stirred at 25° C. for 4 h. Concentration and purification by flash chromatography (2 M NH3 in MeOH/CH2Cl2) provided the desired compound (10 mg). MS (ESI): exact mass calculated for C18H16ClN3, 309.10; found, m/z 310.4 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.37-7.21 (m, 7H), 7.08-7.05 (m, 2H), 5.29 (s, 2H), 4.09 (s, 2H), 4.04 (s, 2H).

Workup

  1. customthe organic layer was separated
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-2ce4304ba4de4a4ba13aae2ade5c0502
Source dataset
uspto-grants-2008_07
Patent number
US07402680B2

Reaction notes

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