p-Toluenesulfonic acid → 2-(1-(4-Bromophenyl)-3-oxocyclobutyl)isoindoline-1,3-dione

HRID 1914845Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:11][C:10]3(OCC[O:12]3)[CH2:9]2)=[CH:4][CH:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:9][C:10](=[O:12])[CH2:11]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of Compound [XXXVI] (3.25 g, 7.85 mmol, 1.0 eg.) in acetone (300 mL), was added p-toluenesulfonic acid (1.49 g, 7.85 mmol, 1.0 eq.) with stirring and heated to 70° C. After 64 hours at 70° C., the reaction was cooled and poured into saturated aqueous NaHCO3 and extracted with ethyl acetate (×3). The combined organic phases were concentrated and the resulting residue purified by silica gel chromatography eluting with heptane and ethyl acetate (gradient of 0% to 40% ethyl acetate) to give Compound [XXXVII]: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.92-4.01 (m, 2H) 4.20-4.33 (m, 2H) 7.44-7.52 (m, 4H) 7.74 (dd, J=5.37, 3.12 Hz, 2H) 7.84 (dd, J=5.54, 3.00 Hz, 2H).

Workup

temperaturethe reaction was cooled
extractionextracted with ethyl acetate (×3)
concentrationThe combined organic phases were concentrated
customthe resulting residue purified by silica gel chromatography
washeluting with heptane and ethyl acetate (gradient of 0% to 40% ethyl acetate)

Sources & evidence

ORD record: ord-f6941d2662a0452d8d8ecacd2bf93adf
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614221B2

Reaction notes

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