Reaktion #168710

Reaktionsgleichung

5-(3-bromo-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

DIPEA

Boc2O

5-(3-bromo-phenyl)-5-fluoromethyl-morpholine-3-thione

t-butyl hydroperoxide

NH4OH

→

title compound

[5-(3-Bromo-phenyl)-6-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Lösungsmittel

dichloromethane

dichloromethane

NH3 MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was quenched with a saturated aqueous solution of Na2S2O3
2. 2
   Extraktionextracted with EtOAc
3. 3
   WaschenThe extract was washed with brine
4. 4
   Trocknendried with sodium sulfate
5. 5
   Sonstigeevaporated
6. 6
   workup.WAITAfter 14 h
7. 7
   Waschenwashed with water, 1N HCl and brine
8. 8
   TrocknenThe organic phase was dried with sodium sulfate
9. 9
   Sonstigeevaporated
10. 10
    SonstigeThe residue was chromatographed on silica gel (cyclohexane/EtOAc=6:1)

Vorschrift

To a solution of 5-(3-bromo-phenyl)-5-fluoromethyl-morpholine-3-thione (200 mg, 0.658 mmol) in 5 ml of 7M NH3/MeOH were added t-butyl hydroperoxide (80%, 0.818 ml, 6.58 mmol) and then 1.7 ml of 25% aqueous NH4OH. After 2 h, the mixture was quenched with a saturated aqueous solution of Na2S2O3 and extracted with EtOAc. The extract was washed with brine, dried with sodium sulfate and evaporated. The crude 5-(3-bromo-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (189 mg, 0.658 mmol) was dissolved in 4 ml of dichloromethane. The solution was treated with DIPEA (0.172 ml, 0.987 mmol) and Boc2O (187 mg, 0.855 mmol). After 14 h, the mixture was diluted with dichloromethane and washed with water, 1N HCl and brine. The organic phase was dried with sodium sulfate and evaporated. The residue was chromatographed on silica gel (cyclohexane/EtOAc=6:1) to yield the title compound. TLC (hexane/EtOAc=6:1): Rf=0.20; HPLC: RtH1=2.380 min; 1H-NMR (400 MHz, CDCl3): 7.56-6.98 (m, 4H; broad signals due to rotamers), 4.80-3.60 (m, 6H), 1.42 (br, 9H); MS: 387, 389 [(M+H)+].

Quelle