Bromothymol Blue → Tetraethyl 3-benzylaminopentane-1,1-bisphosphonate

To a stirred solution of tetraethyl 3-oxopentane-1,1-bisphosphonate (0.50 g, 1.4 mmol) in methanol (5 ml) was added a small amount of bromothymol blue and benzylamine (0.75 g, 7.0 mmol). Acetic acid was added dropwise until the solution turned yellow (pH=6), and NaCNBH3 (57 mg, 0.9 mmol) was added. The resulting yellow solution was stirred at room temperature for 2 days, at which time more NaCNBH3 (20 mg) was added. After stirring a total of 4 days, the reaction was quenched by adding concentrated HCl until the pH was less than 1, and the solvents were removed in vacuo. The residue was taken up in water (10 ml) and washed with diethyl ether (2×20 ml). The aqueous layer was made basic (pH greater than 10) by the addition of solid KOH, saturated with NaCl, and extracted with dichloromethane (5×25 ml). The combined extracts were dried (Na2SO4) and concentrated to give tetraethyl 3-benzylaminopentane-1,1-bisphosphonate. This material was hydrolyzed by heating at reflux in concentrated HCl (6 ml) for 20 hours. The volatiles were removed under vacuum, the residue dissolved in water (10 ml) and concentrated under vacuum to give 0.49 g of Compound No. 159 as a hygroscopic foam.

1. additionwas added
2. additionwas added
3. customthe reaction was quenched
4. additionby adding concentrated HCl until the pH was less than 1
5. customthe solvents were removed in vacuo
6. washwashed with diethyl ether (2×20 ml)
7. additionby the addition of solid KOH
8. extractionsaturated with NaCl, and extracted with dichloromethane (5×25 ml)
9. dry with materialThe combined extracts were dried (Na2SO4)
10. concentrationconcentrated

ORD-Eintrag

ord-ea7684e9a71040288dbea5e299a3c7d7

Quelldatensatz

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05728650