Phthalimide potassium salt → 1,1-Dimethylethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoate

HRID 2382921Notes

Reaction equation

HRID 2382921 reaction equation
[C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[I:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][CH:22]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=2)[CH:23]([CH2:31][CH2:32]OS(C)(=O)=O)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:16][CH:15]=1>CN(C)C=O>[O:6]=[C:4]1[C:3]2[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:1](=[O:11])[N:5]1[CH2:32][CH2:31][CH:23]([CH:22]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=1)[CH2:21][CH2:20][C:17]1[CH:18]=[CH:19][C:14]([I:13])=[CH:15][CH:16]=1)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]

Participants

4

Reactant 2

HCID 24194345Phthalimide potassium saltHCID 578870261,1-Dimethylethyl 5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl)oxy]ethyl}pentanoate

Product 1

HCID 578870191,1-Dimethylethyl 2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoateYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Potassium phthalimide (0.33 g, 2.2 mmol) was added in one portion to a stirred solution of 1,1-dimethylethyl 5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl)oxy]ethyl}pentanoate (1.15 g, 1.86 mmol) in dimethylformamide (6 mL) at room temperature under nitrogen. The resulting solution was heated at 80° C. for 1 h 45 min then cooled to room temperature. The volatiles were evaporated and the residue partitioned between dichloromethane (50 mL) and water (50 mL). The layers were separated and the organic phase evaporated to dryness. The residue was chromatographed on silica gel (50% ethyl acetate:cyclohexane) to give the title compound (0.26 g, 21%) as a yellow oil which was a mixture of diastereoisomers. LC/MS: 4.29 min; z/e 687, calcd (M+18) 687. 1H NMR (400 MHz: CDCl3): 7.85 (2H), 7.70 (2H), 7.55-7.20 (4H), 6.90-6.75 (4H), 4.55-4.30 (2H), 3.80 (3H), 3.75 (1H), 3.65 (2H), 2.80-2.45 (3H), 2.10-1.50 (4H), 1.40 (9H).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe volatiles were evaporated
  3. customthe residue partitioned between dichloromethane (50 mL) and water (50 mL)
  4. customThe layers were separated
  5. customthe organic phase evaporated to dryness
  6. customThe residue was chromatographed on silica gel (50% ethyl acetate:cyclohexane)

Sources & evidence

ORD record
ord-975e1fe81fdf492d9e4b23a89de93b39
Source dataset
uspto-grants-2012_09
Patent number
US08263602B2

Reaction notes

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