Sodium Iodide → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic Acid Ethoxycarbonyloxymethyl Ester

HRID 516476Notes

Reaction equation

HRID 516476 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:22][C:23]([C:25]3[NH:29][C:28](=[O:30])[N:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[N:26]=3)=[O:24])[CH2:16][C@@H:17]([OH:21])[C:18]([OH:20])=[O:19])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:37](=[O:44])([O:41][CH2:42][CH3:43])[O:38][CH2:39]Cl.N1C(C)=CC=CC=1C.[Na+].[I-]>CN(C=O)C>[CH2:42]([O:41][C:37]([O:38][CH2:39][O:19][C:18](=[O:20])[C@H:17]([OH:21])[CH2:16][C@H:15]([NH:22][C:23]([C:25]1[NH:29][C:28](=[O:30])[N:27]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:26]=1)=[O:24])[CH2:14][C:11]1[CH:10]=[CH:9][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)=[CH:13][CH:12]=1)=[O:44])[CH3:43]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 79372,6-LutidineHCID 5325479Chloromethyl Ethyl CarbonateHCID 136344442(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic Acid

Product 1

HCID 136344443(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic Acid Ethoxycarbonyloxymethyl EsterYield 4.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic acid (253 mg, 0.5 mmol), chloromethyl ethyl carbonate (69 mg, 0.5 mmol), 2,6-lutidine (165 mg, 1.5 mmol) and NaI (150 mg, 1 mmol) in DMF (20 mL) was stirred for 15 hours at 50° C. The mixture was quenched with water (20 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were collected and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether/EtOAc=3:1) to yield the title compound as a white solid (13 mg). LC-MS: 608.8 [M+H]+. 1H NMR: (CDCl3, 400 MHz) δ 1.27 (t, J=8.0 Hz, 3H), 2.03-2.33 (m, 2H), 3.02-3.05 (m, 2H), 4.18 (q, J=8.0 Hz, 2H), 4.49 (br, 1H), 4.85 (br, 1H), 5.57-5.76 (m, 2H), 7.03 (d, J=12 Hz, 1H), 7.25-7.40 (m, 4H), 7.42-7.51 (m, 3H), 7.53-7.61 (m, 3H), 7.93 (d, J=8.0 Hz, 2H).

Workup

  1. customThe mixture was quenched with water (20 mL)
  2. extractionextracted with EtOAc (3×30 mL)
  3. customThe combined organic layers were collected
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (petroleum ether/EtOAc=3:1)

Sources & evidence

ORD record
ord-820b0798685247579ae3367c414dd408
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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