Phthalimide potassium salt → 5-Biphenyl-4-yl-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid

HRID 1818861Notes

Reaction equation

HRID 1818861 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].[C:13]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH:21]([O:37]CC2C=CC(OC)=CC=2)[CH:22]([CH2:30][CH2:31]OS(C)(=O)=O)[C:23]([O:25]C(C)(C)C)=[O:24])=[CH:15][CH:14]=1>CN(C)C=O>[C:13]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:14]=[CH:15][C:16]([CH2:19][CH2:20][CH:21]([OH:37])[CH:22]([CH2:30][CH2:31][N:5]2[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]2=[O:6])[C:23]([OH:25])=[O:24])=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 24194345Phthalimide potassium saltHCID 578870321,1-Dimethylethyl 5-(4-biphenylyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl) oxy]ethyl}pentanoate

Product 1

HCID 114306695-Biphenyl-4-yl-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acidYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Potassium phthalimide (8.8 mg, 60 μmol) was added in one portion to a stirred solution of 1,1-dimethylethyl 5-(4-biphenylyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl) oxy]ethyl}pentanoate (28.4 mg, 50 μmol) in dimethylformamide (0.5 mL) under nitrogen at room temperature. 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 taken up in dichloromethane (0.5 mL). Trifloroacetic acid (0.5 mL) was added in one portion and the resulting solution stirred for 1 h at room temperature. The volatiles were evaporated and the residue purified by mass directed auto-preparative HPLC to give the title compound as a white solid (6.0 mg, 27%). LC/MS: 3.43 min; z/e 444, calcd (M+1) 444. 1H NMR (400 MHz: CDCl3): 7.85 (2H), 7.70 (2H), 7.55 (1H), 7.50 (1H), 7.45 (2H), 7.30 (1H), 7.25 (4H), 3.85(3H), 2.95 (1H), 2.75 (1H), 2.60(1H), 2.20 (1H), 2.05 (1H), 1.90 (2H).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe volatiles were evaporated
  3. additionTrifloroacetic acid (0.5 mL) was added in one portion
  4. customThe volatiles were evaporated
  5. customthe residue purified by mass

Sources & evidence

ORD record
ord-0e079771a9334be4a0fc810c3076333d
Source dataset
uspto-grants-2009_10
Patent number
US07601729B2

Reaction notes

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