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

HRID 2364427Notes

Reaction equation

HRID 2364427 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH:8]=O.[NH2:10][C:11]1[C:12]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:13][CH:14]=[C:15]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:16]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(O)(=O)C>[F:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C:15]2[CH:16]=[C:11]([NH:10][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][C:2]3=[O:1])[C:12]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:13][CH:14]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydride2×HCID 22405515(2-Oxopyrrolidin-1-yl)acetaldehydeHCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

Product 1

HCID 58882948Ethyl 5-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethyl]amino}pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 18768099Dichloroethane acetic acidSolvent

Conditions

Temperature
2.5 °C

Procedure

(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+).

Workup

  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

Sources & evidence

ORD record
ord-4e10dd97db36440d8b27cb18526c24bc
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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