Diisopropylcarbodiimide → Tert-butyl 1-(4-(5-(2-(1-phenylcyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

HRID 71229Notes

Reaction equation

HRID 71229 reaction equation
[C:1]1([C:7]2([CH2:13][CH2:14][C:15]([OH:17])=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O/[N:19]=[C:20](/[C:22]1[CH:39]=[CH:38][C:25]([CH2:26][N:27]2[CH2:30][CH:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]2)=[CH:24][CH:23]=1)\[NH2:21].C(N=C=NC(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(#N)C.CCOC(C)=O>[C:1]1([C:7]2([CH2:13][CH2:14][C:15]3[O:17][N:21]=[C:20]([C:22]4[CH:23]=[CH:24][C:25]([CH2:26][N:27]5[CH2:28][CH:29]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:30]5)=[CH:38][CH:39]=4)[N:19]=3)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 3439853-(1-Phenylcyclohexyl)propanoic acidHCID 2724141Tetrabutylammonium FluorideHCID 58504340HCID 58504340, compound2×

Product 1

HCID 66692502Tert-butyl 1-(4-(5-(2-(1-phenylcyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the 3-(1-phenylcyclohexyl)propanoic acid (0.118 g, 0.508 mmol) and the (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Intermediate 1, 0.155 g, 0.508 mmol) in acetonitrile (5.0 mL) at room temperature was added the 1,3-diisopropylcarbodiimide (0.095 mL, 0.609 mmol). The stirring was continued at room temperature and followed by LC/MS. After 90 min., TBAF (0.609 mL, 0.609 mmol) was added to the reaction. The reaction was found to be over after 2 h. The reaction mixture was diluted with EtOAc and washed with water followed by brine. It was then concentrated and purified by preparative HPLC to give the tert-butyl 1-(4-(5-(2-(1-phenylcyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate as a glassy solid. LCMS of the tert-butyl 1-(4-(5-(2-(1-phenylcyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (Conditions: Start % B═O; Final % B=100; Gradient Time=2 min; Flow Rate=5 ml/min; Wavelength=220; Solvent A=10% MeOH—90% H20—0.1% TFA; Solvent B=90% MeOH—10% H2O—0.1% TFA and Column 4=Phenomenex Luna 5u C18 4.6×30 mm (2 min. grad)) (M+H)+=502.39. Retention time=1.927.

Workup

  1. customwas continued at room temperature
  2. customafter 2 h
  3. washwashed with water
  4. concentrationIt was then concentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-a126e12a3f0c4f6299f66afd15266d34
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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