Tetrahydrofuran → 3-{[(1R)-Isobutanoyloxyisobutoxy]carbonylamino}propyl(n-butyl)phosphinic Acid

Temperature

19 °C

To a 3 L three necked round bottom flask fitted with a mechanical stirrer, temperature probe, and nitrogen inlet was added compound (25) (100 mmol), 3-aminopropyl(n-butyl)phosphinic acid (100 mmol), THF (1 L), and water (100 mL). The suspension was stirred under a nitrogen atmosphere at 18-20° C. for 4 h during which time the reaction mixture became homogeneous. The THF was removed in vacuo and the reaction mixture was diluted with methyl tert-butyl ether (250 mL) and washed with 1N HCl (1×500 mL) and water (2×200 mL). The organic phase was separated and concentrated in vacuo to leave a white solid. The solid was purified by flash chromatography to afford the product (39) as a white solid. 1H-NMR (400 MHz, CD3OD): δ 6.74-6.70 (q, J=5.2, 1H), 4.06-3.96 (m, 1H), 3.22-3.21 (m, 2H), 2.547-2.477 (m, 1H), 1.92-1.84 (m, 2H), 1.52-1.48 (s, 3H), 1.142-1.138 (d, J=1.6, 3.0H), 1.124-1.121 (dd, J=1.6, 3.0H). Phosphorus (162 MHz, CD3OD): 51.04; MS (ESI) m/z 346 (M+H)+)

1. customThe THF was removed in vacuo
2. additionthe reaction mixture was diluted with methyl tert-butyl ether (250 mL)
3. washwashed with 1N HCl (1×500 mL) and water (2×200 mL)
4. customThe organic phase was separated
5. concentrationconcentrated in vacuo
6. customto leave a white solid
7. customThe solid was purified by flash chromatography

ORD record

ord-add103e545544aa4935a4cc78db6ecca

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07585996B2