Sodium borohydride → (2,3-Dichloro-4-pyridinyl)methanol

2,3-Dichloro-N-methyl-isonicotinamide (0.353 g, 1.72 mmol) was stirred in 6 mL DCM (not quite homogeneous). tBuONO (0.412 mL, 3.44 mmol) was added followed by the addition of two drops of TFA. After 3 h an additional 0.600 ML tBuONO (5.00 mmol) and three drops TFA were added. The resulting solution was stirred an additional 16 h. An additional 0.400 mL tBuONO (3.34 mmol) and 2 drops TFA were added. After an additional 4.5 h an 0.600 mL tBuONO (5.00 mmol) and 3 drops TFA were added. The reaction was stirred 3 days and was quenched with half-sat NaHCO3 (aq). The mixture was extracted 3× with DCM. The organic phases were dried over Na2SO4, filtered, and concentrated. The slightly impure N-nitrosoamide (0.425 g, 1.82 mmol) was stirred in 5 mL THF. NaBH4 (0.137 g, 3.63 mmol) was added and after 2 h the reaction was slowly quenched with 1M HCl until the bubbling stopped. The solution pH was adjusted to pH 9 with Na2CO3 (s). The mixture was extracted 3× with EtOAc. The organic phases were dried over Na2SO4, filtered, and concentrated to afford the titled compound in good purity. 1H NMR (CDCl3) δ8.32 (d, 1H, J=4.8 Hz), 7.51 (d, 1H, J=5.0 Hz), 4.82 (s, 2H), 2.34 (bs, 1H).

1. additiontBuONO (0.412 mL, 3.44 mmol) was added
2. stirringThe reaction was stirred 3 days
3. customwas quenched with half-sat NaHCO3 (aq)
4. extractionThe mixture was extracted 3× with DCM
5. dry with materialThe organic phases were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customwas slowly quenched with 1M HCl until the bubbling
9. extractionThe mixture was extracted 3× with EtOAc
10. dry with materialThe organic phases were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-d5197f608c40458981c0c5a9b14c391e

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06586423B2