反应 #168710

反应方程式

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

溶剂

dichloromethane

dichloromethane

NH3 MeOH

反应条件

后处理

1. 1
   其他the mixture was quenched with a saturated aqueous solution of Na2S2O3
2. 2
   萃取extracted with EtOAc
3. 3
   洗涤The extract was washed with brine
4. 4
   干燥dried with sodium sulfate
5. 5
   其他evaporated
6. 6
   workup.WAITAfter 14 h
7. 7
   洗涤washed with water, 1N HCl and brine
8. 8
   干燥The organic phase was dried with sodium sulfate
9. 9
   其他evaporated
10. 10
    其他The residue was chromatographed on silica gel (cyclohexane/EtOAc=6:1)

实验过程

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)+].

来源