Sodium triacetoxyborohydride → Ethyl 5-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethyl]amino}pyridine-2-carboxylate

Temperatur

2.5 °C

(2-Oxopyrrolidin-1-yl)acetaldehyde (2.00 g, 15.7 mmol) and ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (2.00 g, 7.32 mmol) were combined in 1:1 dichloroethane/acetic acid (10 mL) and cooled under nitrogen to 0-5° C. Sodium trisacetoxyborohydride (3.10 g, 14.6 mmol) was added and the reaction was stirred for 15 min. Two additional portions of aldehyde (1.0 g, 7.8 mmol) plus sodium triacetoxyborohydride (1.65 g, 7.8 mmol) separated by 15 min. increments were made. The reaction mixture was evaporated in vacuo, dissolved in CH2Cl2, and treated with aqueous K2CO3 (5% w/v). After separating the layers, the aqueous phase was back-extracted twice with CH2Cl2. The combined organic phases were dried over MgSO4, filtered, evaporated in vacuo and purified on silica gel eluting with 0-3% MeOH in EtOAc to provide an oil: 1H NMR (CDCl3) δ 7.89 (1H, d, J=1.4 Hz), 7.83 (1H, br t, J˜6 Hz), 7.15 (2H, dd, J˜9, 6 Hz), 6.98 (2H, t, J˜9 Hz), 6.92 (1H, s), 4.42 (2H, q, J=7 Hz), 3.92 (2H, s), 3.49 (2H, m), 3.41 (2H, t, J=7 Hz), 3.35 (2H, q, J=6 Hz), 2.36 (2H, t, J=8 Hz), 1.99 (2H, m), 1.42 (3H, t, J=7 Hz); ES+ MS: 386 (M+H+).

1. customThe reaction mixture was evaporated in vacuo
2. dissolutiondissolved in CH2Cl2
3. additiontreated with aqueous K2CO3 (5% w/v)
4. customAfter separating the layers
5. extractionthe aqueous phase was back-extracted twice with CH2Cl2
6. dry with materialThe combined organic phases were dried over MgSO4
7. filtrationfiltered
8. customevaporated in vacuo
9. custompurified on silica gel eluting with 0-3% MeOH in EtOAc
10. customto provide an oil

ORD-Eintrag

ord-4e10dd97db36440d8b27cb18526c24bc

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08691991B2