Trimethylsilyldiazomethane → HCID 15895508, compound
Reaction equation
C[Si](C=[N+]=[N-])(C)C.C[O:9][C:10](=[O:36])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18]([C:20]1[C:21]([CH3:35])=[N:22][O:23][C:24]=1[C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1)=[O:19]>>[CH3:35][C:21]1[C:20]([C:18]([NH:17][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C:10]([OH:36])=[O:9])=[O:19])=[C:24]([C:25]2[CH:26]=[CH:27][C:28]([C:31]([F:33])([F:32])[F:34])=[CH:29][CH:30]=2)[O:23][N:22]=1Participants
Procedure
To a heterogeneous mixture of the above carboxylic acid (1.00 g, 4.34 mmol) and anhydrous DMF (2 drops) in anhydrous CH2Cl2 (5 mL) at 0° C. was added dropwise oxalyl chloride (760 μL, 8.69 mmol). The resultant mixture was warmed to RT and stirred for 2.5 h, whereupon it was concentrated to a heterogeneous yellow mixture and purged of excess oxalyl chloride in vacuo. The acid chloride was then added to a homogeneous solution of anthranilic acid (1.19 g, 8.69 mmol) in 2.5 N aqueous NaOH (6.95 mL, 17.4 mmol) at 5° C., resulting in the instantaneous formation of a white precipitate. The reaction mixture was then warmed to RT, whereupon it was diluted with a minimal amount of water to facilitate stirring, which was continued for an additional 1.5 h. The mixture was acidified to pH 2 by addition of concentrated HCl (1.63 mL), diluted with 2.0 N HCl, and stirred for 1.5 h. Filtration of the suspension followed by washing with water, air drying and subsequent recrystallization from MeOH. The title compound which was separated from unreacted starting material by exhaustive methylation of the acid groups with (trimethylsilyl)diazomethane. The isolated 2-{[3-Methyl-5-(4-trifluoromethyl-phenyl)isoxazole-4-carbonyl]-amino}-benzoic acid methyl ester was saponified in a manner similar to Step 2 of this Example to give the title compound (60%): mp (trimethylsilyl)diazomethane. The isolated 2-{[3-Methyl-5-(4-trifluoromethyl-phenyl)-isoxazole-4-carbonyl]-amino}-benzoic acid methyl ester was saponified in a manner similar to Step 2 of this Example to give the title compound (60%): mp 204.6-205.5° C.; 1H NMR (DMSO-d6) δ 13.52 (br s, 1 H), 11.47 (s, 1 H), 8.42 (d, 1 H), 7.97 (ABq, 4 H), 7.93 (dd, 1 H), 7.64 (ddd, 1 H), 7.23 (ddd, 1 H) 2.47 (s, 3 H); IR (KBr) 3374, 3118, 2987, 2656, 1681, 1659, 1604, 1585, 1532, 1441, 1263, 1166, 1075, 1014, 905, 847, 762, 719, 701 cm-1 ; MS (m/z) 380 [M+ ].
Sources & evidence
- ORD record
- ord-17f8462e1e0d4b4c8c9f6cd022eeb917
- Source dataset
- uspto-grants-2000_08
- Patent number
- US06096770
Reaction notes
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