Nitromethane → tert-Butyl {2-nitro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamate

Temperatur

-20 °C

Under argon, 9.75 ml (56 mmol) of N,N-diisopropylethylamine were added slowly dropwise to a suspension of 20.35 g (56 mmol) of zinc(II) trifluoromethanesulphonate in 300 ml of nitromethane at RT and the mixture was stirred for 1 h thereafter. The yellow suspension was subsequently admixed with 13.9 g (84 mmol) of (1R,2S)-(−)-2-(N-methylamino)-1-phenylpropan-1-ol [(−)-N-methylephedrine] and 18.4 g of molecular sieve and stirred for 1 h thereafter, then cooled to −20° C. A dropping funnel was charged with 51.0 g (186.6 mmol) of the compound from Example 11A, with addition of 75 ml of nitromethane. The initial solution underwent spontaneous warming to about 40° C., and the formation of a precipitate began. Thereafter the entire contents of the dropping funnel were added immediately in one portion to the cooled zinc(II) trifluoromethanesulphonate/(−)-N-methylephedrine mixture (no temperature control). The reaction mixture was stirred in a cooling bath (−20° C.) for a further 5 h, and then stirred overnight as well, the temperature slowly rising to 0° C. The work-up was carried out in analogy to variant 1. The crude product was purified using a short silica gel column (eluent dichloromethane/ethanol 100:2). The product-containing fractions were combined and freed from the solvents on a rotary evaporator, and the residue was dried in an HV. The solid obtained was stirred with 200 ml of n-pentane at RT, isolated again by filtration and dried in an HV. This gave 32.4 g of the title compound (approximately 82% purity according to LC-MS, 43% of theory).

1. stirringstirred for 1 h
2. stirringThe reaction mixture was stirred in a cooling bath (−20° C.) for a further 5 h
3. stirringstirred overnight as well, the temperature
4. customslowly rising to 0° C
5. customThe crude product was purified
6. customfreed from the solvents on a rotary evaporator
7. customthe residue was dried in an HV
8. customThe solid obtained
9. customisolated again by filtration
10. customdried in an HV

ORD-Eintrag

ord-3d9e7b188a094fa28e7c43debeb108c6

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08202895B2