Diisopropylcarbodiimide → 3-(4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylphenyl)-5-(3-(6-phenyl-1,4-dioxaspiro[4.5]decan-6-yl)propyl)-1,2,4-oxadiazole

HRID 71253Notes

Reaction equation

HRID 71253 reaction equation
[C:1]1([C:7]2([CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])[CH2:16][CH2:15][CH2:14][CH2:13][C:8]32[O:12][CH2:11][CH2:10][O:9]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:23][C:24]1([CH3:43])[O:28][C@H:27]([CH2:29][O:30][C:31]2[C:40]([CH3:41])=[CH:39][C:34](/[C:35](=[N:37]/O)/[NH2:36])=[CH:33][C:32]=2[CH3:42])[CH2:26][O:25]1.C(N=C=NC(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(#N)C>[CH3:23][C:24]1([CH3:43])[O:28][C@H:27]([CH2:29][O:30][C:31]2[C:32]([CH3:42])=[CH:33][C:34]([C:35]3[N:37]=[C:20]([CH2:19][CH2:18][CH2:17][C:7]4([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH2:16][CH2:15][CH2:14][CH2:13][C:8]54[O:12][CH2:11][CH2:10][O:9]5)[O:21][N:36]=3)=[CH:39][C:40]=2[CH3:41])[CH2:26][O:25]1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 2724141Tetrabutylammonium FluorideHCID 666926294-(6-Phenyl-1,4-dioxaspiro[4.5]decan-6-yl)butanoic acidHCID 87110972(R,Z)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-N'-hydroxy-3,5-dimethyl-benzimidamide

Product 1

HCID 666928363-(4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylphenyl)-5-(3-(6-phenyl-1,4-dioxaspiro[4.5]decan-6-yl)propyl)-1,2,4-oxadiazoleYield 59.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(6-phenyl-1,4-dioxaspiro[4.5]decan-6-yl)butanoic acid (62.0 mg, 0.204 mmol) and (R,Z)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-N′-hydroxy-3,5-dimethylbenzimidamide (50 mg, 0.17 mmol) in acetonitrile (2 mL) was added N,N′-diisopropylcarbodiimide (0.032 mL, 0.204 mmol), and the mixture was stirred for 1 hr at room temp. Then 1M TBAF (0.221 mL, 0.221 mmol) was added, and the mixture was stirred at room temp for 18 hrs. It was partitioned between EtOAc and water, and the aqueous layer was extracted with EtOAc once more. Combined extracts were washed with Na2SO4 and evaporated to give an oily residue. It was purified by Combiflash (24 g silica gel) eluting with 3:7 followed by 1:1 EtOAc-hexane to give 3-(4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylphenyl)-5-(3-(6-phenyl-1,4-dioxaspiro[4.5]decan-6-yl)propyl)-1,2,4-oxadiazole as an oil (57 mg). LC/MS: m/e 563.21 (M+H)+.

Workup

  1. stirringthe mixture was stirred at room temp for 18 hrs
  2. customIt was partitioned between EtOAc and water
  3. extractionthe aqueous layer was extracted with EtOAc once more
  4. washCombined extracts were washed with Na2SO4
  5. customevaporated
  6. customto give an oily residue
  7. customIt was purified by Combiflash (24 g silica gel)
  8. washeluting with 3:7

Sources & evidence

ORD record
ord-957c87e2f559490088975bb6ae725bfd
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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