3-Benzyl-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine → 3-(3-Methyl-1-phenylcyclobutyl)-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine

HRID 1581700Notes

Reaction equation

HRID 1581700 reaction equation
[CH2:1]([C:8]1[N:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:11]2=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>BrCC(C)CCl>[CH3:1][CH:2]1[CH2:7][C:1]([C:8]2[N:12]3[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:11]3=[N:10][N:9]=2)([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:3]1

Participants

3

Reactant 1

HCID 227221323-Benzyl-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine

Product 1

HCID 227221273-(3-Methyl-1-phenylcyclobutyl)-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine

Reagents, catalysts & solvents 1

HCID 955661-Bromo-3-chloro-2-methylpropaneSolvent

Conditions

Temperature
-40 °C

Procedure

3-Benzyl-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine (287.6 mg) and 1-bromo-3-chloro-2-methylpropane (140 μL) were dissolved in anhydrous, deoxygenated tetrahydrofuran, and the solution was cooled to −40° C. under an argon atmosphere. Potassium bis(trimethylsilyl)amide (KHMDS, 0.5M in toluene, 2.5 mL) was added dropwise. After 30 minutes, a second aliquot of KHMDS (2.5 mL) was added. After 30 additional minutes, KHMDS (2.15 mL) was added again, and the solution was allowed to slowly warm to room temperature. After one hour, the reaction was quenched with water and added to brine. After extraction with ethyl acetate, the organic layer was dried with magnesium sulfate, filtered, evaporated and purified by silica gel chromatography to give 3-[1-(4-chlorophenyl)-(Z)-3-(methoxymethoxy)cyclobutyl]-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine (4-10) as a ca. 1.2:1 mixture of isomers.

Workup

  1. customdeoxygenated tetrahydrofuran
  2. additionPotassium bis(trimethylsilyl)amide (KHMDS, 0.5M in toluene, 2.5 mL) was added dropwise
  3. additiona second aliquot of KHMDS (2.5 mL) was added
  4. additionAfter 30 additional minutes, KHMDS (2.15 mL) was added again
  5. temperatureto slowly warm to room temperature
  6. waitAfter one hour
  7. customthe reaction was quenched with water
  8. additionadded to brine
  9. extractionAfter extraction with ethyl acetate
  10. dry with materialthe organic layer was dried with magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-37ca41423f1a4a199a5e330a067fad5c
Source dataset
uspto-grants-2004_05
Patent number
US06730690B2

Reaction notes

Loading…