Dichloromethane → HCID 11522057, compound

N-Boc-2-(4-methoxybenzyl)morpholine was prepared using the same procedure as described for example 9, intermediate (a), but starting with racemic epichlorohydrin. N-Boc-2-(4-methoxybenzyl) (0.16 mmol) was dissolved in dichloromethane (1.5 mmol) and N-bromosuccinimide (28 mg, 0.16 mmol) added. The reaction was shaken for 18 hrs at room temperature and then further N-bromosuccinimide (11 mg, 0.06 mmol) added. The reaction was shaken for a further 2 hrs, Na2S2O3 (10% w/v aqueous solution, 1 mL) added and the mixture shaken for 40 minutes. The mixture was poured on to an HMN column (25 g) and washed with dichloromethane (10 mL) and the liquors concentrated in vacuo. The residue was dissolved in dichloromethane (1.5 mL), treated with TFA (1 mL) and shaken for 90 minutes at room temperature. The reaction mixture was added directly to an SCX-2 column (5 g) and washed with dichloromethane (2 mL×2) and methanol (2 mL). The SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL and 2×2.5 mL). Combined ammonia washes were concentrated in vacuo. The residue was dissolved in IPA (2 mL) and diethyl ether (2 mL) and treated with MP-carbonate (3.1 mmol/g, 300 mg) and shaken for 30 minutes. The suspensions were filtered and the concentrated in vacuo to yield the desired 2-(3-Bromo-4-methoxy-benzyl)-morpholine example 72, as a beige gum (18 mg).

1. stirringThe reaction was shaken for a further 2 hrs
2. stirringthe mixture shaken for 40 minutes
3. additionThe mixture was poured on to an HMN column (25 g)
4. washwashed with dichloromethane (10 mL)
5. concentrationthe liquors concentrated in vacuo
6. dissolutionThe residue was dissolved in dichloromethane (1.5 mL)
7. additiontreated with TFA (1 mL)
8. stirringshaken for 90 minutes at room temperature
9. additionThe reaction mixture was added directly to an SCX-2 column (5 g)
10. washwashed with dichloromethane (2 mL×2) and methanol (2 mL)
11. washThe SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL and 2×2.5 mL)
12. concentrationCombined ammonia washes were concentrated in vacuo
13. dissolutionThe residue was dissolved in IPA (2 mL)
14. additiondiethyl ether (2 mL) and treated with MP-carbonate (3.1 mmol/g, 300 mg)
15. stirringshaken for 30 minutes
16. filtrationThe suspensions were filtered
17. concentrationthe concentrated in vacuo

ORD record

ord-859e2ac1cf7e4fe19002feb6c96febf4

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07323466B2