Reaction #47280

Reaction equation

2-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-isoindole-1,3-dione

methylamine

Heptane

→

1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine

Yield 94.6%

Solvents

methyl t-butyl ether

ethanol

ethanol

Conditions

Workup

1. 1
   Temperaturewas cooled with an ice water bath
2. 2
   Temperaturethe mixture was cooled (−20° C.) for 30 min
3. 3
   OtherThe resulting solids were removed by filtration
4. 4
   Washrinsed with heptane
5. 5
   ConcentrationThe filtrate was partially concentrated to a volume of ˜50 mL
6. 6
   OtherThe resulting solids were removed by filtration
7. 7
   Washrinsed with methyl t-butyl ether and heptane
8. 8
   workup.DISSOLUTIONwhich was then dissolved in methyl t-butyl ether (15 mL)
9. 9
   Temperaturecooled (−20° C.) for 30 min
10. 10
    workup.ADDITIONAddition of seed crystals
11. 11
    Othercrystallization of the product
12. 12
    workup.ADDITIONHeptane (30 mL) was added
13. 13
    Temperaturethe suspension was cooled (−20° C.) for 30 min
14. 14
    FiltrationSubsequent filtration
15. 15
    Washwashing with heptane, and suction
16. 16
    Otherdrying

Procedure

A suspension of 2-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-isoindole-1,3-dione (5.00 g, 15.3 mmol) in methyl t-butyl ether (50 mL) and ethanol (30 mL) was cooled with an ice water bath, and 33 wt. % methylamine in ethanol (20.0 mL, 161 mmol) was added. After 30 min, the mixture was warmed to room temperature and stirred for 2 h. Heptane (50 mL) was added and the mixture was cooled (−20° C.) for 30 min. The resulting solids were removed by filtration and rinsed with heptane. The filtrate was partially concentrated to a volume of ˜50 mL. The resulting solids were removed by filtration and rinsed with methyl t-butyl ether and heptane. After concentration of the filtrate to dryness, a yellow oil remained, which was then dissolved in methyl t-butyl ether (15 mL) and cooled (−20° C.) for 30 min. Addition of seed crystals and scratching with a spatula initiated crystallization of the product. Heptane (30 mL) was added and the suspension was cooled (−20° C.) for 30 min. Subsequent filtration, washing with heptane, and suction drying afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (2.85 g, 94.6%) as a white solid: LR-ES-MS m/z calculated for C9H15N3O2 [M]+ 197, observed [M+H]+ 198.

Source