Methyl iodide → 1-Methyl-4-(4-nitro-benzyl)-1,2,3,6-tetrahydro-pyridine

4-(4-Nitrobenzyl)pyridine (64 g) and TBAI (6 g) were dissolved in CH2Cl2 (500 mL) and the solution was suspended with NaOH (aq. 5N, 450 mL) in a 3 L 3-necked round bottom flask. With vigorous stirring, CH3I (213 g) was added and stirred vigorously at RT for 60 h (or until blue color disappears). The reaction was quenched with dimethylamine (100 mL) and MeOH (300 mL) and stirred for 2 h. NaBH4 (19 g) was added to the mixture in small portions. The reaction mixture was stirred for 30 min at RT, then partitioned between CH2Cl2/H2O (500 mL/500 mL). The organic layer was collected and the aqueous layer was washed with CH2Cl2 (300 mL×3). The combined organic layers was washed with brine then concentrated in vacuo. The residue was purified on a silica wash-column (7% TEA in EtOAc). The desired fractions were combined and concentrated under vacuum to give the desired compound as a dark gray solid. (MS: M+1=261).

1. customThe reaction was quenched with dimethylamine (100 mL) and MeOH (300 mL)
2. stirringstirred for 2 h
3. additionNaBH4 (19 g) was added to the mixture in small portions
4. stirringThe reaction mixture was stirred for 30 min at RT
5. custompartitioned between CH2Cl2/H2O (500 mL/500 mL)
6. customThe organic layer was collected
7. washthe aqueous layer was washed with CH2Cl2 (300 mL×3)
8. washThe combined organic layers was washed with brine
9. concentrationthen concentrated in vacuo
10. customThe residue was purified on a silica wash-column (7% TEA in EtOAc)
11. concentrationconcentrated under vacuum

ORD record

ord-d192fee6cb634734950e151d17a435b1

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247430B2