Triethylamine → 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

HRID 1972470Notes

Reaction equation

HRID 1972470 reaction equation
[O:1]=[C:2]1[CH2:9][CH:8]2[N:10]([CH2:11][C@H:12]3[CH2:17][N:16](C([O-])=O)[CH2:15][CH2:14][N:13]3C([O-])=O)[CH:4]([CH2:5][O:6][CH2:7]2)[CH2:3]1.[OH:24][CH:25]1[CH2:32][CH:31]2[N:33]([CH2:34][C@H:35]3[CH2:40][N:39](C([O-])=O)[CH2:38][CH2:37][N:36]3C([O-])=O)[CH:27]([CH2:28][O:29][CH2:30]2)[CH2:26]1.O1CCOCC1.C(N(CC)CC)C.[N+:60]([C:63]1[S:67][C:66]([S:68](Cl)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61]>CCOC(C)=O.Cl.C(Cl)Cl>[N+:60]([C:63]1[S:67][C:66]([S:68]([N:16]2[CH2:15][CH2:14][NH:13][C@@H:12]([CH2:11][N:10]3[CH:8]4[CH2:9][CH:2]([OH:1])[CH2:3][CH:4]3[CH2:5][O:6][CH2:7]4)[CH2:17]2)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61].[N+:60]([C:63]1[S:67][C:66]([S:68]([N:39]2[CH2:38][CH2:37][NH:36][C@@H:35]([CH2:34][N:33]3[CH:31]4[CH2:32][C:25](=[O:24])[CH2:26][CH:27]3[CH2:28][O:29][CH2:30]4)[CH2:40]2)(=[O:70])=[O:69])=[CH:65][CH:64]=1)([O-:62])=[O:61]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 217873475-Nitrothiophene-2-sulfonyl chlorideHCID 86670350(2S)-2-((7-oxo-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylateHCID 86670351(2S)-2-((7-hydroxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate

Product 2

HCID 665826279-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-oneHCID 706562379-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A 100-mL round-bottomed flask was charged with (2S)-2-((7-oxo-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate and (2S)-2-((7-hydroxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate (endo) (0.5 g) in EtOAc (20 mL) and 4N HCl in dioxane (0.85 mL, 3.4 mmol) was added. The reaction was heated to 70° C. for 2 h and after this time the precipitate was filtered, collected and dried. This material was dissolved in CH2Cl2 (10 mL). Triethylamine (0.75 mL, 5.4 mmol) followed by 5-nitrothiophene-2-sulfonyl chloride (0.26 g, 1.13 mmol, Enamine Building Blocks, Kiev, Ukraine) as a solution in CH2Cl2 (5 mL) were then added. After 10 min at room temperature, the reaction was concentrated onto silica and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (0.54 g).

Workup

  1. additionwas added
  2. filtrationafter this time the precipitate was filtered
  3. customcollected
  4. customdried
  5. dissolutionThis material was dissolved in CH2Cl2 (10 mL)
  6. additionwere then added
  7. concentrationthe reaction was concentrated onto silica
  8. custompurified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-6adb357220bd4774b02cab9578e88527
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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