N,N'-Dimethylethylenediamine → (1R,2R)-methyl-3-bromo-5-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)benzoate

HRID 1805349Notes

Reaction equation

HRID 1805349 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[NH:12][C:11]3=[O:19])[CH2:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].CNCCNC.[CH3:32][O:33][C:34](=[O:43])[C:35]1[CH:40]=[C:39](I)[CH:38]=[C:37]([Br:42])[CH:36]=1>[Cu]I.C(#N)C>[CH3:32][O:33][C:34](=[O:43])[C:35]1[CH:40]=[C:39]([N:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C@:10]3([CH2:9][C@@H:8]3[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:11]2=[O:19])[CH:38]=[C:37]([Br:42])[CH:36]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 21942573Methyl 3-bromo-5-iodobenzoateHCID 67233978(1R,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58305415(1R,2R)-methyl-3-bromo-5-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)benzoateYield 48%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A Schlenk tube charged with CuI (214 mg, 1.124 mmol, 20 mmol %), (1S,2S) and (1R,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (1.50 g, 5.62 mmol) and K2CO3 (2.30 g, 16.86 mmol) was evacuated and backfilled with argon. N,N′-dimethylethylenediamine (242 μL, 2.25 mmol, 40 mol %), 3-Bromo-5-iodo-benzoic acid methyl ester (2.30 g, 6.75 mmol, 1.2 equiv.) and acetonitrile (5 mL) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred at 90° C. for 3 hours. HPLC monitor the reaction finished. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (gradient elution, 5-15% ethyl acetate in petroleum ether) to give the title compound as white powder (1.3 g, 48%). LC/MS m/e calcd. for C24H17BrClNO3: 482, observed (M+H)+: 483.

Workup

  1. customwas evacuated
  2. customThe Schlenk tube was sealed with a Teflon valve
  3. customThe solvent was removed under reduced pressure
  4. customThe residue was purified by flash column chromatography (gradient elution, 5-15% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-5b675d313f65475f9f0e49dd95d39a36
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

Loading…