Reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:12][C:11]=1[Cl:21])=[O:9])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].O.[CH3:34][C:35]#[N:36]>>[C:1]([O:5][C:6]([C:7]1[C:35]([C:34]2[CH:11]=[CH:10][CH:8]=[CH:7][CH:6]=2)=[N:36][O:9][C:8]=1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:12][C:11]=1[Cl:21])=[O:22])([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 4
Product 1
Procedure
Intermediate 56 (115 mg, 0.35 mmol) is dissolved in MeCN (3 mL). Potassium bis(trimethylsilyl)amide (106 mg, 0.53 mmol) is added slowly while stirring at room temperature. Then the mixture is cooled to 0° C., and a solution of intermediate 58 (55 mg, 0.35 mmol) in CH3CN (1 mL) is added. The mixture is stirred at room temperature overnight, then H2O (5 mL) is added and the mixture is extracted with DCM (3×10 mL). After concentration the crude product is purified on reverse phase HPLC (H2O/MeCN gradient) to afford 5-(2-chloro-4-methoxycarbonylmethyl-phenyl)-3-phenyl-isoxazole-4-carboxylic acid tert-butyl ester 59 as a white solid: 1H-NMR (400 MHz, CDCl3) δ=7.73 (m, 2H), 7.47 (m, 5H), 7.33 (m, 1H), 3.72 (s, 3H), 3.68 (s, 2H), 1.23 (s, 9H). MS calculated for C23H23ClNO5 (M+H+) 428.1, found 428.1.
Workup
- temperatureThen the mixture is cooled to 0° C.
- stirringThe mixture is stirred at room temperature overnight
- extractionthe mixture is extracted with DCM (3×10 mL)
- concentrationAfter concentration the crude product
- customis purified on reverse phase HPLC (H2O/MeCN gradient)
Sources & evidence
- ORD record
- ord-9dba909da1734a5288f9b1aeb9070b87
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07820705B2
Linked notes
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