Benzyl chloroformate → 1-Carbobenzyloxyamino-2-methylpropanephosphonous acid

Temperature

0 °C

1-(diphenylmethylamino)-2-methylpropylphosphonous acid (12 g) was suspended in 100 mL of 48% hydrobromic acid, then heated at 100° C. for 2 hours until two distinct phases separated. The mixture was evaporated to dryness in vacuo, and the residue taken up in 100 mL of water. The aqueous solution was washed several times with ether to remove diphenylmethyl bromide and then evaporated to give an 80 mL solution of 1-amino-2-methylpropylphosphonous acid, a compound of formula (Xd). The solution of 1-amino-2-methylpropylphosphonous acid in 80 ml water was adjusted to pH 9.5 using 4 N NaOH, and the solution was cooled to 0° C. by an ice bath. Benzyl chloroformate (7.1 mL, 47 mmol) was added dropwise over 30 minutes and the resulting mixture was stirred for an additional 12 hours while the pH was maintained at pH 9-9.5 by periodic addition of 4 N NaOH. The reaction mixture was washed with ether (3×100 mL) to remove excess benzyl chloroformate. The aqueous solution was acidified using concentrated HCl to pH 1, then extracted by ethyl acetate (4×100 mL). The organic phase was dried over Na2SO4 and concentrated to afford 9.2 g of 1-(benzyloxycarbonylamino)-2-methylpropylphosphonous acid, as a white solid, which could be used in further reactions without further purification.

1. washThe reaction mixture was washed with ether (3×100 mL)
2. customto remove excess benzyl chloroformate
3. extractionextracted by ethyl acetate (4×100 mL)
4. dry with materialThe organic phase was dried over Na2SO4
5. concentrationconcentrated

ORD record

ord-bb2bb2207c5c4ea98bef3908d25149dc

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008325B2