HuagongsheHuagongshe Chemistry Print Report · For research reference only
Water → Tert-butyl (r)-4-fluoro-3-[[[n-(benzyloxycarbonyl)-norvalinyl]methylamino]methyl]benzoate
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Water | HCID 962 | — |
| Reactant | Triethylamine | HCID 8471 | — |
| Reactant | 1-Hydroxybenzotriazole | HCID 75771 | — |
| Reactant | 1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride | HCID 2723939 | — |
| Reactant | Z-D-Nva-OH | HCID 10106192 | — |
| Reactant | 1,1-Dimethylethyl 4-fluoro-3-[(methylamino)methyl]benzoate | HCID 11791275 | — |
| Solvent | dichloromethane N,N-dimethylformamide | HCID 22350042 | — |
| Product | Tert-butyl (r)-4-fluoro-3-[[[n-(benzyloxycarbonyl)-norvalinyl]methylamino]methyl]benzoate | HCID 131723731 | 97.3% |
Reaction Steps
According to the procedure of Preparation 4(c), except using tert-butyl 4-fluoro-3-(methylaminomethyl)benzoate (4.00 g, 16.7 mmole), N-(benzyloxycarbonyl)-D-norvaline (4.20 g, 16.7 mmole), HOBt.H2O (2.3 g, 17 mmole), Et3N (2.4 mL, 17.1 mmole), EDC HCl (3.3 g, 17.2 mmole), and 1:1 DMF/CH2Cl2 (100 mL), the title compound (7.68 g, 97%) was prepared as a thick yellow oil following flash chromatography on silica gel (30% EtOAc/hexanes): 1H NMR (300 MHz, DMSO-d6) mixture of amide rotamers δ 7.81-7.92 (m, 1 H), 7.70-7.80 (m, 1 H), 7.52-7.65 (m, 1 H), 7.25-7.38 (m, 5 H), 4.62-5.08 (m, 3 H), 4.38-4.53 (m, 2 H), 2.83 & 3.07 (2 s, 3 H), 1.52-1.58 (m, 2 H), 1.52 (s, 9 H), 1.15-1.37 (m, 2 H), 0.74 & 0.87 (2 t, 3 H).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US06503903B1 |
| Source dataset | uspto-grants-2003_01 |
| ORD ID | ord-44561ccfd22944bc9ef4dce9d9af1b92 |
| Source note | uspto-grants-2003_01 |