Cyclohexanol → (5-Cyclohexyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl ester

HRID 2060419Notes

Reaction equation

HRID 2060419 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([OH:16])[CH:12]=2)[C:7]1=[O:17])[CH3:2].[CH:19]1(O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:12]=2)[C:7]1=[O:17])[CH3:2]

Participants

5

Reactant 3

HCID 7966CyclohexanolHCID 11776TriphenylphosphineHCID 66712563(5-Hydroxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl ester

Product 1

HCID 66712801(5-Cyclohexyloxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl esterYield 58.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (5-hydroxy-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetic acid ethyl ester (8.0 g) in anhydrous tetrahydrofuran (160 ml) was added cyclohexanol (3.2 g), diethylazadicarboxylate (6.9 g) and then triphenyl phosphine (12.6 g). Resulting mixture was stirred at room temperature overnight and concentrated. Residue was partitioned between water and ethyl acetate. Aqueous layer was extracted with ethyl acetate. Combined organic layers were washed with brine, dried over magnesium sulfate and filtered. Filtrate was concentrated and purified by silica gel chromatography (eluting with 5% ethyl acetate in methylene chloride) to give the title compound (6.2 g). 1H NMR (200 MHz, CDCl3) δ 7.73 (dd, J=8.2, 0.8 Hz, 1H), 7.30 (br s, 1H), 7.12 (m, 1H), 4.38 (m, 3H), 4.21 (q, J=7.1 Hz, 2H), 2.02 (m, 2H), 1.82-1.25 (m, 13H).

Workup

  1. customResulting mixture
  2. concentrationconcentrated
  3. customResidue was partitioned between water and ethyl acetate
  4. extractionAqueous layer was extracted with ethyl acetate
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationFiltrate was concentrated
  9. custompurified by silica gel chromatography (eluting with 5% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-f58663755b814c1884d1f7280ea07562
Source dataset
uspto-grants-2012_10
Patent number
US08278325B2

Reaction notes

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