Sodium Chloride → Iodide Ion

HRID 525856Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][O:8][C:9]2[C:10](=[O:27])[CH:11]=[C:12]3[C:17](=[O:18])[N:16]([CH2:19][CH2:20][N:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[CH2:15][CH2:14][N:13]3[CH:26]=2)=[CH:5][CH:4]=1.[C:30]([O:34][C:35]([NH:37][C:38]1[S:39][CH:40]=[C:41](/[C:43](=[N:71]/[O:72][C@@H:73]([CH2:86][C:87]([O:89][C:90]([CH3:93])([CH3:92])[CH3:91])=[O:88])[C:74]([O:76][CH2:77][C:78]2[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][CH:79]=2)=[O:75])/[C:44]([NH:46][C@@H:47]2[C:54](=[O:55])[N:53]3[C@@H:48]2[S@:49](=O)[CH2:50][C:51]([CH2:68][I:69])=[C:52]3[C:56]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][C:63]([O:66][CH3:67])=[CH:62][CH:61]=2)=[O:57])=[O:45])[N:42]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31].P(Br)(Br)Br.[Cl-].[Na+]>CN(C)C(=O)C.CN(C)C=O>[C:90]([O:89][C:87](=[O:88])[CH2:86][C@H:73]([O:72]/[N:71]=[C:43](/[C:41]1[N:42]=[C:38]([NH:37][C:35]([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:36])[S:39][CH:40]=1)\[C:44]([NH:46][C@@H:47]1[C:54](=[O:55])[N:53]2[C@@H:48]1[S:49][CH2:50][C:51]([CH2:68][N+:21]1([CH2:20][CH2:19][N:16]3[CH2:15][CH2:14][N:13]4[CH:26]=[C:9]([O:8][CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:29][CH:28]=5)[C:10](=[O:27])[CH:11]=[C:12]4[C:17]3=[O:18])[CH2:22][CH2:23][CH2:24][CH2:25]1)=[C:52]2[C:56]([O:58][CH2:59][C:60]1[CH:61]=[CH:62][C:63]([O:66][CH3:67])=[CH:64][CH:65]=1)=[O:57])=[O:45])[C:74]([O:76][CH2:77][C:78]1[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][CH:79]=1)=[O:75])([CH3:93])([CH3:91])[CH3:92].[I-:69]

Participants

Conditions

Temperature: 40 °C

Procedure

To the heat gun dried flask under nitrogen was added 7-((4-methoxybenzyl)oxy)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,8(2H)-dione (700 mg, 1.761 mmol) in N,N-dimethylacetamide (DMA) (10 mL) followed by (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((5R,6R,7R)-3-(iodomethyl)-2-(((4-methoxybenzyl)oxy)carbonyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-2-oxoethylidene)amino)oxy)succinate (Example 1h) (1828 mg, 1.761 mmol) in N,N-dimethylacetamide (DMA) (10 mL). Mixture was heated at 40° C. for 3 h. Cooled and stored in fridge overnight. The mixture was cooled to −40° C. and N,N-dimethylformamide (DMF) (10 mL) was added followed by phosphorus tribromide (0.332 mL, 3.52 mmol) dropwise over 10 min. Stirred at −40° C. for 30 min. Poured into the cooled solution of 5% sodium chloride. The resulting solid was filtered and dried to give crude 1-(((6R,7R)-7-((Z)-2-((((S)-4-(tert-butoxy)-1-((4-methoxybenzyl)oxy)-1,4-dioxobutan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-(((4-methoxybenzyl)oxy)carbonyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl)-1-(2-(7-((4-methoxybenzyl)oxy)-1,8-dioxo-3,4-dihydro-1H-pyrido[1,2-a]pyrazin-2(8H)-yl)ethyl)pyrrolidin-1-ium, Iodide (2.6 g, 1.832 mmol, 104% yield). LCMS: (M+H)+: 1420.8

Workup

customTo the heat gun dried flask under nitrogen
temperatureCooled
temperatureThe mixture was cooled to −40° C.
filtrationThe resulting solid was filtered
customdried

Sources & evidence

ORD record: ord-ac10aa33e7764a6084f904ede28cffc6
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340556B2

Reaction notes

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