Phthalimide → Tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-4-fluoropiperidine-1-carboxylate

HRID 2112548Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:16])([CH2:14]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[C:50]1(=[O:60])[NH:54][C:53](=[O:55])[C:52]2=[CH:56][CH:57]=[CH:58][CH:59]=[C:51]12>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:14][N:54]2[C:50](=[O:60])[C:51]3[C:52](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:53]2=[O:55])([F:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

After dissolving 4-fluoro-4-(hydroxymethyl)piperidinecarboxylic acid tert-butyl ester (4.26 g, 18.3 mmol) in THF (183 mL), the solution was cooled to 0° C. Triphenylphosphine (7.19 g, 27.4 mmol) and DIAD (diisopropyl azodicarboxylate) (5.39 mL, 27.4 mmol) were then added to the solution. After stirring for 20 minutes, phthalimide (4.03 g, 27.4 mmol) was added and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated, and the crude product was crudely purified by silica gel column chromatography (20% AcOEt/hexane) to obtain 4-[(1,3-dioxoisoindolin-2-yl)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester.

Workup

stirringthe mixture was stirred at room temperature for 2.5 hours
concentrationThe reaction mixture was concentrated
customthe crude product was crudely purified by silica gel column chromatography (20% AcOEt/hexane)

Sources & evidence

ORD record: ord-6d2b33a7aea048c89769bb84f083782c
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07524841B2

Reaction notes

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