Lithium Hexamethyldisilazide → {4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetic acid

HRID 219932노트

반응식

HRID 219932 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[C:26]([F:39])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1Cl>CC(C)CO.C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[C:26]([F:39])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1[O:23][CH2:19][CH:14]([CH3:15])[CH3:13]

참가 물질

5

반응물 2

HCID 2733832Lithium HexamethyldisilazideHCID 86645655Tert-butyl {4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetate

생성물 1

HCID 59495678{4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetic acid

시약·촉매·용매 2

HCID 6560Isobutanol용매HCID 8028Tetrahydrofuran용매

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온도
130 °C

실험 절차

Lithium bis(trimethylsilyl)amide (225 μl; 1 M; 0.22 mmol) was added to a solution of tert-butyl {4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetate (66.04 mg; 0.15 mmol) in 2-methyl-1-propanol (1.50 mL) and THF (2 mL). The resulting mixture was heated at 130° C. for 10 min in the microwave. A mixture of the desired product and the isopropyl ester was isolated. NaOH (5N solution; 5 eq; 0.15 mL) was added and the mixture was stirred at RT for 2 hours. The reaction mixture was diluted with EtOAc and washed with HCl 1N, brine and dried over MgSO4. After evaporation of the solvents, the title product was isolated as white solid (51 mg; 81%). 1H NMR (DMSO-d6, 300 MHz) δ 13.25 (br s, 1H), 8.91 (d, J=2 Hz, 1H), 8.57 (d, J=2 Hz, 1H), 7.90-7.86 (m, 2H), 7.32 (t, J=9 Hz, 1H), 4.91 (s, 2H), 4.27 (d, J=6 Hz, 2H), 2.12 (m, 1H), 1.02 (d, J=6 Hz, 6H). LC/MS (Method B): 420.3 (M−H)−. HPLC (Method A) Rt 5.29 min (Purity: 100%).

출처 및 근거

ORD 기록
ord-1fb00fc435ea49e39aba0a9b884ab9a2
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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