Tetrahydrofuran → HCID 57513839, compound

HRID 2368433Notes

Reaction equation

HRID 2368433 reaction equation
C(OC(=O)[NH:10][C:11]([C:14](=[O:35])[NH:15][C:16]1[N:20]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[N:18]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:17]=1)([CH3:13])[CH3:12])C1C=CC=CC=1.C1COCC1>Br.O.CCOC(C)=O.CO>[NH2:10][C:11]([CH3:13])([CH3:12])[C:14]([NH:15][C:16]1[N:20]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[N:18]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:17]=1)=[O:35]

Participants

6

Reactant 2

HCID 8028TetrahydrofuranHCID 57513765HCID 57513765, compound

Product 1

HCID 57513839HCID 57513839, compound

Reagents, catalysts & solvents 3

HCID 260Hydrogen BromideSolventHCID 962WaterSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
0 °C

Procedure

A flask containing {1-[1-Benzyl-5-(4-fluoro-phenyl)-1H-[1,2,4]triazol-3-ylcarbamoyl]-1-methyl-ethyl}-carbamic acid benzyl ester (777 mg, 1.59 mmol) was chilled to 0° C. The solid was dissolved in 48% aqueous HBr (5 mL) and the mixture stirred at 0° C. After 10 min the mixture was allowed to warm to room temp. After 5.5 hr THF (5 mL) was added and the mixture was stirred for 2 days. The reaction was diluted with water (30 mL) and extracted with Et2O (2×50 mL). The pH of the aqueous phase was adjusted to 10 by addition of 4N NaOH. The basic aqueous phase was extracted with Et2O (2×50 mL). The organics from the second extraction were combined and dried with brine (15 mL) followed by Na2SO4. Concentration resulted in a brown oil. The oil was dissolved in EtOAc/MeOH and the solvent evaporated to yield the title compound as a white solid: 1H NMR (400 MHz, ACETONITRILE-d3) 1.53 (s, 6H) 5.38 (s, 2H) 7.08-7.19 (m, 2H) 7.19-7.28 (m, 2H) 7.28-7.39 (m, 3H) 7.60-7.69 (m, 2H); Rt (method A)=0.96 min (M+H)+=354.2.

Workup

  1. temperatureto warm to room temp
  2. stirringthe mixture was stirred for 2 days
  3. extractionextracted with Et2O (2×50 mL)
  4. additionThe pH of the aqueous phase was adjusted to 10 by addition of 4N NaOH
  5. extractionThe basic aqueous phase was extracted with Et2O (2×50 mL)
  6. extractionThe organics from the second extraction
  7. dry with materialdried with brine (15 mL)
  8. concentrationConcentration
  9. customresulted in a brown oil
  10. customthe solvent evaporated

Sources & evidence

ORD record
ord-750711bec3bc4a078fd7b55ceded9eb8
Source dataset
uspto-grants-2014_04
Patent number
US08703761B2

Reaction notes

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