Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Triethylamine | HCID 8471 | — |
| Reactant | 4-Cyano-2-fluorobenzoic acid | HCID 590659 | — |
| Reactant | Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 9886157 | — |
| Reactant | 4-N-Boc-2-hydroxymethylpiperazine | HCID 22386508 | — |
| Solvent | Water | HCID 962 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Solvent | Ethyl Acetate | HCID 8857 | — |
| Product | HCID 58180879 | HCID 58180879 | 78.6% |
Reaction Steps
Triethylamine (892 μL, 6.40 mmol) was added to a mixture of 4-cyano-2-fluorobenzoic acid (275 mg, 1.66 mmol, Alfa Aesar) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (580 mg, 1.52 mmol) in THF (13 mL). After stirring for 15 min, tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (0.30 g, 1.4 mmol, racemic, AstaTech) was added. The reaction was stirred overnight. Ethyl acetate and water were added, the mixture shaken, and layers separated. The organic layer was washed with water, 0.1N NaOH, and brine; dried over sodium sulfate, decanted and concentrated. Flash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes afforded the racemic product as a white solid (400 mg, 71%). 1H NMR (300 MHz, CDCl3): δ 7.61-7.38 (m, 3H), 4.90-2.51 (m, 9H), 1.47 (s, 9H); LCMS (M-tBu+2H)+: 308.1.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09249145B2 |
|---|
| Source dataset | uspto-grants-2016_02 |
|---|
| ORD ID | ord-e87f640ab13f4b3f91e8621ebf6827bb |
|---|
| Source note | uspto-grants-2016_02 |
|---|
