Phthalic Anhydride → 1H-Isoindole-1,3(2H)-dione, 2-[(1R)-2-hydroxy-1-phenylethyl]-

HRID 709435Notes

Reaction equation

[NH2:1][C@H:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][OH:4].[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12>CC#N>[OH:4][CH2:3][C@H:2]([N:1]1[C:14](=[O:15])[C:13]2[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]1=[O:16])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a 2.0-5.0 mL microwave vial was added (R)-2-amino-2-phenylethan-1-ol (1.53 g, 0.0112 mol) and phthalic anhydride (1.65 g, 0.0112 mol). The reaction mixture was capped and heated to 150° C. for 2 minutes in a microwave reactor. The mixture was cooled and diluted with CH3CN (2 mL), recapped and heated in the microwave reactor a second time at 140° C. for 20 minutes. The volatiles were removed under reduced pressure and the resulting solid was suspended in EtOAc (50 mL). The organic layer was washed with 5% NaHCO3 (aq), H2O, and brine, dried with anhydrous MgSO4 and concentrated. The crude residue was purified by flash chromatography (silica gel, eluting with CH3OH in CH2Cl2 (0 to 5%) to yield 2.81 g (94%) of the title compound. LC/MS: m/z (ES+) 268 (M+H)+.

Workup

customThe reaction mixture was capped
temperatureThe mixture was cooled
temperatureheated in the microwave reactor a second time at 140° C. for 20 minutes
customThe volatiles were removed under reduced pressure
washThe organic layer was washed with 5% NaHCO3 (aq), H2O, and brine
dry with materialdried with anhydrous MgSO4
concentrationconcentrated
customThe crude residue was purified by flash chromatography (silica gel
washeluting with CH3OH in CH2Cl2 (0 to 5%)

Sources & evidence

ORD record: ord-f3f00e6b29734919a2382577ac393684
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181200B2

Reaction notes

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