Benzylamine → 2-Benzyl-2,3-dihydro-1H-isoindole

HRID 1625303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625303
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1[CH2:13][CH2:12][CH2:11][CH2:10]1>C(N(CC)CC)C>[CH2:1]([N:8]1[CH2:4][C:3]2[C:11](=[CH:12][CH:13]=[CH:1][CH:2]=2)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

4

Edukt 2

HCID 7504BenzylamineHCID 8028Tetrahydrofuran

Produkt 1

HCID 14027062-Benzyl-2,3-dihydro-1H-isoindole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

In Scheme 7A, the commercially available bis-bromomethyl benzoic acid ester ((LI) is reacted with benzylamine in a polar aprotic solvent such as tetrahydrofuran (THF) in the presence of a non-interfering base such as triethylamine to give the N-benzyl dihydroisoindole intermediate (LII). The ester group in intermediate (LII) is then reduced to the corresponding alcohol using lithium aluminium hydride in THF to give the hydroxymethyldihydroisoindole intermediate (LIII). Debenzylation of the hydroxymethyldihydroisoindole intermediate (LIII) is then carried out by hydrogenation over palladium on charcoal catalyst in an alcohol (e.g. ethanol) solvent at a mildly elevated temperature (e.g. up to about 50°) to give the intermediate (LIV). Intermediate (LIV) is then converted to intermediate (LV) by reaction with a reagent suitable for introducing a benzyloxycarbonyl (“Z”) group onto the nitrogen atom of the dihydroisoindole ring. For example, the intermediate (LIV) can be reacted with benzyl chloroformate in a polar non-protic solvent such as THF in the presence of a non-interfering base such as triethylamine to give intermediate (LV).

Quellen und Nachweise

ORD-Eintrag
ord-43b008f782af4bd6ac3c2040116de6c0
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08779132B2

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