Allyl bromide → (r)-2-(3-Bromo-4-(prop-2-en-1-yloxy)benzyl)morpholine

Temperature

55 °C

N-BOC-(R)-2-(3-bromo-4-hydroxybenzyl)morpholine, example 4, intermediate (a) (70 mg, 0.19 mmol) was dissolved in acetone (1.5 mL), treated with potassium carbonate (78 mg, 0.56 mmol) and allyl bromide (68 mg, 1.86 mmol) added. The resulting reaction was shaken at 55° C. for 16 hrs. The reaction was filtered and concentrated under a flow of nitrogen. The crude residue was dissolved in tetrahydrofuran (8 mL) with polymer supported diphenylphosphine (0.5 g) and shaken for 4 hrs. The reaction was then filtered and concentrated under a high flow of nitrogen. The crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.5 mL) and shaken for 3 hrs at room temperature. The reaction mixture was added directly to an SCX-2 column (2 g) and washed with dichloromethane (2 mL×2) and methanol (2 mL×2). The SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL). Combined ammonia washes were concentrated in vacuo to yield the desired morpholine example 19 as a colorless oil (35 mg).

1. additionadded
2. customThe resulting reaction
3. filtrationThe reaction was filtered
4. concentrationconcentrated under a flow of nitrogen
5. dissolutionThe crude residue was dissolved in tetrahydrofuran (8 mL) with polymer
6. stirringshaken for 4 hrs
7. filtrationThe reaction was then filtered
8. concentrationconcentrated under a high flow of nitrogen
9. dissolutionThe crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.5 mL)
10. stirringshaken for 3 hrs at room temperature
11. additionThe reaction mixture was added directly to an SCX-2 column (2 g)
12. washwashed with dichloromethane (2 mL×2) and methanol (2 mL×2)
13. washThe SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL)
14. concentrationCombined ammonia washes were concentrated in vacuo

ORD record

ord-0b57d5a040c54f118cee8bef1c420cc8

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07323466B2