Water → ethyl 3-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)propanoate

HRID 660434Notes

Reaction equation

HRID 660434 reaction equation
N[C:2]1[N:3]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([CH:23]3[CH2:25][CH2:24]3)=[CH:15][CH:14]=2)[C:4]([S:7][CH2:8][CH2:9][C:10]([O-:12])=[O:11])=[N:5][N:6]=1.N([O-])=O.[Na+].Cl[CH:31](Cl)[C:32](O)=O.O.C(Br)(Br)[Br:38]>[Br-].C([N+](CC)(CC)CC)C1C=CC=CC=1.ClCCl>[Br:38][C:2]1[N:3]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([CH:23]3[CH2:24][CH2:25]3)=[CH:15][CH:14]=2)[C:4]([S:7][CH2:8][CH2:9][C:10]([O:12][CH2:31][CH3:32])=[O:11])=[N:5][N:6]=1

Participants

8

Reactant 5

HCID 962Water2×HCID 5558BromoformHCID 6597Dichloroacetic AcidHCID 23668193Sodium NitriteHCID 866330723-(5-Amino-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)propanoate

Product 1

HCID 46178847ethyl 3-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)propanoateYield 47.6%

Reagents, catalysts & solvents 2

HCID 165294Benzyltriethylammonium bromideCatalystHCID 6344DichloromethaneSolvent

Procedure

3-(5-Amino-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)propanoate, (200 mg 0.523 mmol), sodium nitrite (361 mg, 5.233 mmol, 10 eq.) and benzyltriethylammonium bromide (427 mg, 1.570 mmol, 3 eq.) were suspended in bromoform (3 mL) and stirred at room temperature for ˜30 min. Dichloroacetic acid was then added (86 μL, 135 mg; 1.047 mmol, 2 eq.), and the mixture stirred at room temperature overnight, covering the flask with foil to keep light out. Water was added (5 mL) and stirring continued for a further 30 min. The reaction mixture was then transferred to a sep. funnel and additional water and dichloromethane were added. The organic layer was collected and the aqueous layer washed with dichloromethane (2×). The combined organic extracts were dried over sodium sulfate, filtered, concentrated and purified by flash column chromatography (6:4 Hexanes/Ethyl acetate) to give ethyl 3-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)propanoate as a light brown oil (111 mg, 47.6%).

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. stirringstirring
  3. waitcontinued for a further 30 min
  4. customThe organic layer was collected
  5. washthe aqueous layer washed with dichloromethane (2×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (6:4 Hexanes/Ethyl acetate)

Sources & evidence

ORD record
ord-4d166ef3bfe64ef5933bfa8cbe9a0201
Source dataset
uspto-grants-2011_12
Patent number
US08084483B2

Reaction notes

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