Benzyl chloroformate → Isoindoline

To a solution of 1-(2-allyloxy-5-chloro-phenyl)-5-fluoro-2-(2-methyl-propane-2-sulfinyl)-2,3-dihydro-1H-isoindole (230 mg, 0.56 mmol, 1.0 eq.) in MeOH (10 mL), 4M HCl in dioxane (2 mL) was added. The mixture was stirred at r.t. for 2 hours. The reaction mixture was concentrated in vacuo. To a solution of the residue and DIPEA (0.30 mL, 1.69 mmol, 3.0 eq.) in DCM (10 mL), benzyl chloroformate (0.10 mL, 0.68 mmol, 1.2 eq.) was added. The mixture was stirred at r.t. for 4 hours. The reaction mixture was diluted with 1M aq. citric acid soln. (10 mL). The layers were separated. The aq. phase was extracted with DCM (2×10 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired isoindoline.

1. concentrationThe reaction mixture was concentrated in vacuo
2. stirringThe mixture was stirred at r.t. for 4 hours
3. customThe layers were separated
4. extractionThe aq. phase was extracted with DCM (2×10 mL)
5. washphases were washed with sat. aq. NaCl soln
6. dry with material(1×10 mL), dried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by prep
9. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

ORD record

ord-6c345636aea84099a7fccb65c4747dcc

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575158B2