(3-(((tert-Butoxycarbonyl)amino)(phenyl)methyl)phenoxy)acetic acid → Tert-butyl((3-((3-(4-((1,3-dioxolan-2-yl)methyl)phenyl)-1,2,4-oxadiazol-5-yl)methoxy)phenyl)(phenyl)methyl)carbamate

HRID 332697Notes

Reaction equation

HRID 332697 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:16]=[CH:15][C:10]([C:11](=[N:13][OH:14])[NH2:12])=[CH:9][CH:8]=1.[C:17]([O:21][C:22]([NH:24][CH:25]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][CH:36]=1)[O:29][CH2:30][C:31](O)=O)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C(#N)C.N1C=CC=CC=1.[Cl-].[Na+].O>[C:17]([O:21][C:22](=[O:23])[NH:24][CH:25]([C:26]1[CH:36]=[CH:35][CH:34]=[C:28]([O:29][CH2:30][C:31]2[O:14][N:13]=[C:11]([C:10]3[CH:15]=[CH:16][C:7]([CH2:6][CH:2]4[O:3][CH2:4][CH2:5][O:1]4)=[CH:8][CH:9]=3)[N:12]=2)[CH:27]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 2

HCID 71093126(3-(((tert-Butoxycarbonyl)amino)(phenyl)methyl)phenoxy)acetic acidHCID 866769114-((1,3-Dioxolan-2-yl)methyl)-N'-hydroxybenzimidamide

Product 1

HCID 71113095Tert-butyl((3-((3-(4-((1,3-dioxolan-2-yl)methyl)phenyl)-1,2,4-oxadiazol-5-yl)methoxy)phenyl)(phenyl)methyl)carbamate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of 4-((1,3-dioxolan-2-yl)methyl)-N′-hydroxybenzimidamide (0.747 g, 3.35 mmol) and 2-(3-(((tert-butoxycarbonyl)amino)(phenyl)methyl)phenoxy)-acetic acid (Example 59 Step 2, 1.0 g, 2.79 mmol)) in acetonitrile (5 mL), was added 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.8 g, 4.18 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with pyridine (1 mL) and heated at 150° C. for 30 minutes in a microwave. The reaction was diluted with saturated brine and extracted with ethyl acetate (×3). The combined organic fractions were dried with magnesium sulphate, and the solvent evaporated at reduced pressure. Material used directly in the next step without further purification (1.01 g, 65%).

Workup

  1. temperatureheated at 150° C. for 30 minutes in a microwave
  2. extractionextracted with ethyl acetate (×3)
  3. dry with materialThe combined organic fractions were dried with magnesium sulphate
  4. customthe solvent evaporated at reduced pressure
  5. customMaterial used directly in the next step without further purification (1.01 g, 65%)

Sources & evidence

ORD record
ord-f4c39570920442a9b805b54aa1c1ac57
Source dataset
uspto-grants-2014_11
Patent number
US08877774B2

Reaction notes

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