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(S)-N-[3-(3-Fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide → N-[((5S)-3-{4'-[5-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-4,5-dihydroisoxazol-3-yl]-2-fluoro-1,1'-biphenyl-4-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

HRID 747221
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HRID 747221 반응식
[Si:1]([O:8][CH2:9][CH:10]1[O:14][N:13]=[C:12]([C:15]2[CH:20]=[CH:19][C:18]([Sn](C)(C)C)=[CH:17][CH:16]=2)[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:25][C:26]1[CH:27]=[C:28]([N:33]2[CH2:37][C@H:36]([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[O:35][C:34]2=[O:43])[CH:29]=[CH:30][C:31]=1I>O1CCOCC1>[Si:1]([O:8][CH2:9][CH:10]1[O:14][N:13]=[C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:31]3[CH:30]=[CH:29][C:28]([N:33]4[CH2:37][C@H:36]([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[O:35][C:34]4=[O:43])=[CH:27][C:26]=3[F:25])=[CH:17][CH:16]=2)[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
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4

반응물 2

HCID 11222662(S)-N-[3-(3-Fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideHCID 597494295-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-3-[4-(trimethylstannyl)phenyl]4,5-dihydroisoxazole2회

생성물 1

HCID 59749422N-[((5S)-3-{4'-[5-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-4,5-dihydroisoxazol-3-yl]-2-fluoro-1,1'-biphenyl-4-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide수율 33.4%

시약·촉매·용매 1

HCID 31275
1,4-Dioxane
용매

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온도
90 °C

실험 절차

5-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-3-[4-(trimethylstannyl)phenyl]4,5-dihydroisoxazole (427 mg, 0.94 mmol), N-{[(5S)-3-{3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (355 mg, 0.96 mmol) and 2-trifurylphosphine (22 mg, 0.094 mmol) were dissolved in dry 1,4-dioxane (10 ml) and the reaction mixture placed under an atmosphere of argon. Tris(dibenzylidineacetone)dipalladium (0) chloroform adduct (49 mg, 0.05 mmol) was added and the reaction mixture stirred for 16 hours at 90° C. A second portion of 5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-[4-(trimethylstannyl)phenyl]-4,5-dihydroisoxazole (427 mg, 0.94 mmol), 2-trifurylphosphine (22 mg, 0.094 mmol) and tris(dibenzylidineacetone)dipalladium (0) chloroform adduct (49 mg, 0.05 mmol) were added and the reaction mixture stirred for another 20 hours at 90° C. Silica gel (2 g) was added and the mixture concentrated in vacuo. Purification by column chromatography (20 g silica gel bond elut: 30% to 100% ethyl acetate/hexanes) yielded 170 mg (33%) of the desired compound.

후처리

  1. stirringthe reaction mixture stirred for another 20 hours at 90° C
  2. additionSilica gel (2 g) was added
  3. concentrationthe mixture concentrated in vacuo
  4. customPurification by column chromatography (20 g silica gel bond elut: 30% to 100% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-b5c601f73953499cb887d4d4192a25de
출처 데이터셋
uspto-grants-2008_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07396847B2

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