Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Triethylamine | HCID 8471 | — |
| Reactant | 1,1'-Carbonyldiimidazole | HCID 68263 | — |
| Reactant | Proline benzyl ester hydrochloride | HCID 2733413 | — |
| Reactant | HCID 54211279 | HCID 54211279 | — |
| Reactant | Water ammonium hydroxide | HCID 86589665 | — |
| Solvent | Isopropanol | HCID 3776 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Solvent | DCM MeOH AcOH | HCID 21877243 | — |
| Product | HCID 131714445 | HCID 131714445 | — |
Reaction Steps
A solution of (S)-[[2-(benzoylamino)-4-methylpentyl]hydroxyphosphinyl]acetic acid (0.85 g., 2.60 mmole) in dry tetrahydrofuran (10 ml.) at 0° (ice bath) under argon was treated with carbonyldiimidazole (0.50 g., 3.08 mmole). After one hour, the mixture was treated with triethylamine (1.0 ml., 7.23 mmole), and L-proline, phenylmethyl ester, hydrochloride salt (0.75 g., 3.1 mmole), allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between ethyl acetate-5% potassium bisulfate. The ethyl acetate layer was washed successively with 5% potassium bisulfate, 5% sodium biphosphate (pH 4.5 buffer) and saturated sodium chloride, dried (MgSO4) and evaporated. The residue (1.3 g.) was taken up in 1N lithium hydroxide (2.5 ml.), diluted with saturated sodium bicarbonate (30 ml.) and washed with ether (twice). The aqueous phase was acidified with concentrated hydrochloric acid (pH 1) and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with saturated sodium chloride, dried (MgSO4) and evaporated to give 0.9 g. of (S)-1-[[[2-(benzoylamino-4-methylpentyl]hydroxyphosphinyl]acetyl]-L-proline, phenylmethyl ester as a white foam. Rf (acetic acid/methanol/dichloromethane; 1:1:20)=0.25; Rf (isopropanol/conc. NH4OH/water; 7:2:1)=0.74.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US04716155 |
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| Source dataset | uspto-grants-1987_12 |
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| ORD ID | ord-89a3cfcb9a0847b591c19c035c12b974 |
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| Source note | uspto-grants-1987_12 |
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