Lithium Hydroxide → 3-Methyl-1,2-oxazole-5-carbonyl chloride

HRID 553009Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 553009
ClC1C=CC(N(CC)C([C@@H]2C3C(=CC=CC=3)N([C:21]([C:23]3[O:27][N:26]=[C:25]([CH3:28])[CH:24]=3)=[O:22])[C@@H](C)C2)=O)=CC=1.FC(F)(F)C1C=CC(C([Cl:40])=O)=CC=1.CC1C=C(C(O)=O)ON=1.C(Cl)(=O)C(Cl)=O.[OH-].[Li+].C(OC(C1ON=C(C)C=1)=O)C>C(Cl)Cl.CN(C)C=O>[CH3:28][C:25]1[CH:24]=[C:23]([C:21]([Cl:40])=[O:22])[O:27][N:26]=1

Komponenten

9

Edukt 6

HCID 3939Lithium HydroxideHCID 65578Oxalyl chlorideHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 8530853-Methylisoxazole-5-carboxylic acidHCID 103294873-Methylisoxazole-5-carboxylic acid ethyl esterHCID 58732723(+/-)-trans-2-Methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide

Produkt 1

HCID 129050993-Methyl-1,2-oxazole-5-carbonyl chloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(±)-trans-2-Methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide was made following general procedure A, substituting 3-methyl-isoxazole-5-carbonyl chloride for 4-trifluoromethyl-benzoyl chloride. 3-Methyl-isoxazole-5-carbonyl chloride was prepared by reaction of the preformed 3-methyl-isoxazole-5-carboxylic acid with oxalyl chloride and dimethylformamide in methylene chloride. In addition, only 1.2 equivalents of lithium hydroxide were used in the ester hydrolysis step. The crude 2-methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide was isolated as a mixture of cis and trans isomers. Purification by silica gel chromatography (dichloromethane/methanol gradient: 99.5/0.5->99/1) yielded (±)-trans-methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (24%). 1H-NMR (CDCl3) δ: 1.02 (t, 3H), 1.13 (d, 3H), 1.40-1.50 (m, 1H), 2.25 (s, 3H), 2.70-2.80 (m, 1H), 3.40-3.52 (m, 1H), 3.80 (q, 2H), 4.95-5.10 (m, 1H), 6.35 (d, 1H), 6.42 (s, 1H), 6.70 (d, 1H), 6.90 (t, 1H), 7.00 (t, 1H), 7.10 (d, 2H), 7.40 (d, 2H). MS m/z: 438/440 (M+1).

Aufarbeitung

  1. customThe crude 2-methyl-1-(3-methyl-isoxazole-5-carbonyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide was isolated as a mixture of cis and trans isomers

Quellen und Nachweise

ORD-Eintrag
ord-76dda217ebaa415d91d2a4dd8231672e
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951950B2

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