Water → (R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine

HRID 1051198Notes

Reaction equation

HRID 1051198 reaction equation
[CH3:1][C:2]1([CH3:17])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13]C(=O)C)=[N:9]2)[CH2:4][O:3]1.O.[OH-].[Na+].CCCCCCC>C(OC)(C)(C)C>[CH3:1][C:2]1([CH3:17])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH2:13])=[N:9]2)[CH2:4][O:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 8900HeptaneHCID 14798Sodium HydroxideHCID 76903180HCID 76903180, compound

Product 1

HCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineYield 85.2%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
62.5 °C

Procedure

To a 5 L glass flask equipped with a mechanical stirrer and thermometer was charged with 584 g (315 g after corrected by wt %, 1.28 mol) of N-[1-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-acetamide and 1.2 L of purified water. The mixture was agitated at 60-65° C. for 3 h, forming a homogeneous solution. After cooling the batch to 40-45° C., 214 g (5.14 mol) of NaOH (solid) was added in portions. The mixture was agitated at 90° C. for 24 h. The mixture was cooled to 20-25° C. and extracted with 2 kg of isopropyl acetate. The combined organic phase was concentrated by distillation in vacuo (35-45° C. (batch)/P<−0.1 MPa) to give a yellow oil. The residue was diluted with 414 g of methyl tert-butyl ether and 750 g of heptane subsequently. The resulting suspension was stirred at 20-25° C. for 15 h. The solids were collected by filtration and washed with 1100 g of methyl tert-butyl ether/heptane (1/2, v/v). The solids were dried in a vacuum oven (30-35° C./P≦−0.1 MPa) for ca. 24 h to afford 215 g (68% yield in 2 steps) of 1-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine as an off-white solid. 1H-NMR (400 MHz, d6-DMSO): δ 7.31 (s, 1H), 5.38 (s, 1H), 4.55 (s, 2H), 4.26-4.32 (m, 1H), 3.92-3.98 (m, 3H), 3.7-3.73 (m, 1H), 1.31 (s, 3H), 1.25 (s, 3H).

Workup

  1. customTo a 5 L glass flask equipped with a mechanical stirrer
  2. customforming a homogeneous solution
  3. temperatureAfter cooling the batch to 40-45° C.
  4. stirringThe mixture was agitated at 90° C. for 24 h
  5. temperatureThe mixture was cooled to 20-25° C.
  6. extractionextracted with 2 kg of isopropyl acetate
  7. concentrationThe combined organic phase was concentrated by distillation in vacuo (35-45° C. (batch)/P<−0.1 MPa)
  8. customto give a yellow oil
  9. stirringThe resulting suspension was stirred at 20-25° C. for 15 h
  10. filtrationThe solids were collected by filtration
  11. washwashed with 1100 g of methyl tert-butyl ether/heptane (1/2
  12. customThe solids were dried in a vacuum oven (30-35° C./P≦−0.1 MPa) for ca. 24 h

Sources & evidence

ORD record
ord-7c7229c66cb04c36b404f91c3657b6f7
Source dataset
uspto-grants-2016_07
Patent number
US09388168B2

Reaction notes

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