Formaldehyde → 2-(4-Bromophenyl)-1-methylpyrrolidine

To a suspension of 2-(4-bromophenyl)pyrrolidine hydrogen chloride (200 mg, 0.76 mmol) in anhydrous MeOH (5 mL) was added formaldehyde (114 mg, 3.80 mmol) under N2. The mixture was stirred at room temperature for 2 h under N2. After 2 h, NaBH(OAc)3 (242 mg, 1.14 mmol) was added and the mixture was stirred at room temperature under N2 overnight. Additional formaldehyde (2 mL) and NaBH(OAc)3 (242 mg, 1.14 mmol) were then added and the mixture was stirred at room temperature for 5 hrs. The reaction was concentrated and water was added (20 mL) with dichloromethane (8 mL). The layers were separated and the water was extracted with dichloromethane (8 mL×3). The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated to afford the title compound (0.203 g, quantitative yield) which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.51 (d, 2H), 7.28 (d, 2H), 3.15-3.10 (t, 1 H), 3.04-3.00 (t, 1 H), 2.22-2.18 (q, 1H), 2.13-2.09 (m, 1H), 2.05 (s, 3H), 1.80-1.65 (m, 2H), 1.53-1.50 (m, 1H).

1. waitAfter 2 h
2. stirringthe mixture was stirred at room temperature under N2 overnight
3. stirringthe mixture was stirred at room temperature for 5 hrs
4. concentrationThe reaction was concentrated
5. additionwater was added (20 mL) with dichloromethane (8 mL)
6. customThe layers were separated
7. extractionthe water was extracted with dichloromethane (8 mL×3)
8. washwashed with brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated

ORD record

ord-d811bd16b6fb4e6496c32881ce4911a1

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394285B2