Chloroacetyl chloride → HCID 16639031, compound

0.82 g of chloroacetyl chloride (7.3 mmol) and 0.81 g (8.0 mmol) of triethylamine were added to a solution of (+/−)-norgalanthamine (2.0 g, 7.3 mmol) in dry TRF (100 ml). The reaction mixture was refluxed for 3 hours and concentrated by evaporation. The residue was diluted with 2N hydrochloric acid (100 ml) and extracted with EtOAc (3×75 ml). The aqueous phase was set at pH>8.5 with concentrated ammonia and extracted with 3×75 ml of CH2Cl2. The combined, organic phases were washed with common salt solution, dried on sodium sulfate and concentrated by evaporation. Flash chromatography yielded 0.20 g (7.7% of compound 4j): 1H-NMR (CDCl3) δ 6.78 (b, 1H), 6.12 (m, 2H), 5.30 (d, J=11.0 Hz, 1H), 4.65 (m, 2H), 4.32–4.01 (m, 3H), 3.78 (s, 3H), 3.59 (m, 1H), 3.06 (m, 1H), 2.61 (d, J=16.0 Hz, 1H), 1.90 (m, 3H), 13C-NMR (CDCl3) δ 166.0 (s) 146.2 (s), 144.9 (s), 132.3 (d), 128.3 (s), 127.3 (s), 126.0 (d), 120.2 (d), 111.2 (d), 88.2 (d), 61.7 (d), 55.8 (q), 52.8 (t), 48.1 (s), 45.5 (t), 41.4 (t), 35.4 (t), 29.6 (t).

1. temperatureThe reaction mixture was refluxed for 3 hours
2. concentrationconcentrated by evaporation
3. additionThe residue was diluted with 2N hydrochloric acid (100 ml)
4. extractionextracted with EtOAc (3×75 ml)
5. extractionextracted with 3×75 ml of CH2Cl2
6. washorganic phases were washed with common salt solution
7. customdried on sodium sulfate
8. concentrationconcentrated by evaporation

ORD record

ord-645359a94a0f4a48aac15169cec28db9

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07166588B2