Diisopropylethylamine → (9H-fluoren-9-yl)methyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate

HRID 1406874Notes

Reaction equation

HRID 1406874 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:17][N:18]1[C:24](=[O:25])[N:23]2[CH2:26][C@H:19]1[CH2:20][CH2:21][C@H:22]2[C:27]1[O:31][N:30]=[C:29]([CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[N:28]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:38](ON1C(=O)CCC1=O)([O:40][CH2:41][CH:42]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[C:48]2[C:43]1=[CH:44][CH:45]=[CH:46][CH:47]=2)=[O:39]>C1COCC1>[CH2:10]([O:17][N:18]1[C:24](=[O:25])[N:23]2[CH2:26][C@H:19]1[CH2:20][CH2:21][C@H:22]2[C:27]1[O:31][N:30]=[C:29]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][CH2:41][CH:42]3[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:48]=4[C:49]4[C:54]3=[CH:53][CH:52]=[CH:51][CH:50]=4)=[O:39])[CH2:34][CH2:33]2)[N:28]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 86700692(2S,5R)-6-(benzyloxy)-2-(3-(piperidin-4-yl)-1,2,4-oxadiazol-5-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one

Product 1

HCID 86700694(9H-fluoren-9-yl)methyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIPEA (1.6 mL, 10.0 mmol) was slowly added dropwise to a solution of (2S,5R)-6-(benzyloxy)-2-(3-(piperidin-4-yl)-1,2,4-oxadiazol-5-yl)-1,6-diaza-bicyclo[3.2.1]octan-7-one (1.1 g, 2.0 mmol) in THF (50 mL) at 0° C. The mixture was stiffed under N2 atmosphere at 0° C. for 15 minutes, then, Fmoc-OSu (2.4 g, 7.2 mmol) was added and the mixture was stirred at rt. for 8 hrs. The mixture was concentrated and the residue was purified by silica gel column chromatography (gradient elution 1:6 to 1:2 EtOAc/hexanes) to give (9H-fluoren-9-yl)methyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate (1.0 g, 86%) as a white solid.

Workup

  1. waitfor 8 hrs
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by silica gel column chromatography (gradient elution 1:6 to 1:2 EtOAc/hexanes)

Sources & evidence

ORD record
ord-ccd6c15296ec4d58b313c5c6d25578ad
Source dataset
uspto-grants-2014_12
Patent number
US08916709B2

Reaction notes

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