Acetic Anhydride → HCID 22857071, compound

Acetic anhydride (73.5 g) was chilled and stirred as 98% formic acid (44.2 g) was added over 30 minutes keeping the temperature below 10° C. The resulting solution of acetic-formic anhydride was stirred for a further 15 minutes at 5° C. and added over 5 minutes to a stirred, chilled solution of (S)(+)-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine (26 g) in 98% formic acid (26 ml). The reaction solution was stirred at ambient temperature for 1 hour, poured into an ice-water mixture (200 g) and basified with 10N aqueous sodium hydroxide solution (about 250 ml) to pH 10; the mixture was then extracted with dichloromethane (3×200 ml). The combined extracts were back-washed with 1N aqueous hydrochloric acid (100 ml ), then water (100 ml), and evaporated under vacuum to give the title compound (28.69 g, 94%) as a solid, m.p. 52°-54° C.; Rf 0.80 (silica; chloroform, methanol; 95:5). A chiral HPLC assay on an acetylated β-cyclodextrin column showed this material to be a 94:6 mixture of the (S)- and (R)-enantiomers, respectively.

1. additionwas added over 30 minutes
2. customthe temperature below 10° C
3. additionadded over 5 minutes to a stirred
4. extractionthe mixture was then extracted with dichloromethane (3×200 ml)
5. washThe combined extracts were back-washed with 1N aqueous hydrochloric acid (100 ml )
6. customwater (100 ml), and evaporated under vacuum

ORD record

ord-efcb27863ff04860b684a0c76a49696d

Source dataset

uspto-grants-1995_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05463126