Hydroxylamine → 1,2-Benzisoxazole

HRID 82876

Reaktionsgleichung

Reaktionsgleichung von HRID 82876
[C:1](C1C=CC=CC=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:15][NH2:16].CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(O)C>[O:15]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH:1]=[N:16]1

Komponenten

6

Edukt 4

HCID 787HydroxylamineHCID 3102BenzophenoneHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylate

Produkt 1

HCID 710731,2-Benzisoxazole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

FIG. 17B shows the synthesis of the simplified benzophenone subunit. Compound 18 in FIG. 17B was conveniently prepared from commercial available 3-fluoro-4-methoxyacetophenone through Baeyer-Villiger oxidation followed by deacetation and subsequent protection with MOM group. MOM-directed ortholithiation followed by aryllithium addition to commercially available aldehyde 19 provided barbinol 20 in moderate yield. Similarly, Oxidation of barbinol 20 with active manganese dioxide gave the crucial intermediate 21. Unmasking the carboxyl group of 21 with NaOH afforded acid 22. To introduce the desired side chain R, 21 was first treated with HCl to remove MOM group and introduction of R followed by the treatment of NaOH gave the desired benzophenone acid 24. Benzisoxazole acid 25 was prepared from benzophenone 23 by a three-step sequence in which oxime formation was accomplished with hydroxyl-amine in ethanol and dehydration with diethylazodicarboxylate and triphenyl phosphine followed by hydrolysis of the methyl ester furnished the final product 25. See FIG. 17B.

Quellen und Nachweise

ORD-Eintrag
ord-3833a6814ee54e898f9a27a9d2547012
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846742B2

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