(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 747221Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 90 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-b5c601f73953499cb887d4d4192a25de
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07396847B2

Reaction notes

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