Toluene-4-sulfonic acid tetrahydro-furan-3-ylmethyl ester → 2-[(Oxolan-3-yl)methyl]-1H-isoindole-1,3(2H)-dione

HRID 913295Notes

Reaction equation

CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][CH2:16][O:15][CH2:14]2)(=O)=O)=CC=1.[C:18]1(=[O:28])[NH:22][C:21](=[O:23])[C:20]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]12.[K]>CN(C)C=O>[O:15]1[CH2:16][CH2:17][CH:13]([CH2:12][N:22]2[C:18](=[O:28])[C:19]3[C:20](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:21]2=[O:23])[CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (tetrahydro-3-furanyl)methyl 4-methylbenzenesulfonate (i.e., the product of Step A) (11.0 g, 42.9 mmol) in N,N-dimethylformamide (160 mL) was added potassium phthalimide (7.9 g, 42.7 mmol) in one portion, and the resulting mixture was stirred at 80° C. for 6 h. Additional potassium phthalimide (5 g, 27 mmol) was added, and stirring was continued at 100° C. for 18 h. The cooled reaction mixture was partitioned between water and ethyl acetate and the aqueous layer was separated and extracted with ethyl acetate (5×75 mL). The combined extracts were dried over MgSO4 and filtered, and the solvent was removed under reduced pressure to give a residue which was chromatographed on silica gel (40 g) eluted with 5% to 100% ethyl acetate in hexanes to give 4.5 g of the title compound as a white solid, m.p. 114-118° C.

Workup

stirringstirring
waitwas continued at 100° C. for 18 h
customThe cooled reaction mixture
customwas partitioned between water and ethyl acetate
customthe aqueous layer was separated
extractionextracted with ethyl acetate (5×75 mL)
dry with materialThe combined extracts were dried over MgSO4
filtrationfiltered
customthe solvent was removed under reduced pressure
customto give a residue which
customwas chromatographed on silica gel (40 g)
washeluted with 5% to 100% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-3ec3dab14f2a4574ba3e843825dff5c2
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026359B2

Reaction notes

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