Sodium triacetoxyborohydride → HCID 86645055, compound

HRID 2380863Notes

Reaction equation

HRID 2380863 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[N:7]2[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]2)=O.[CH3:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]2([C:32]#[N:33])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:21]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[C:32]([C:26]1([C:22]2[CH:21]=[C:20]([CH3:19])[CH:25]=[CH:24][N:23]=2)[CH2:31][CH2:30][N:29]([CH2:1][C:3]2[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[N:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH2:28][CH2:27]1)#[N:33]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 20634151Ethyl 1-formyl-4-oxo-4H-quinolizine-3-carboxylateHCID 533632764-(4-Methylpyridin-2-yl)piperidine-4-carbonitrile

Product 1

HCID 86645055HCID 86645055, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A mixture of the ethyl 1-formyl-4-oxo-4H-quinolizine-3-carboxylate (2.60 g, 10.6 mmol), 4-(4-methylpyridin-2-yl)piperidine-4-carbonitrile (1.78 g, 8.83 mmol), and 36.8 mL of anhydrous THF was cooled to 10° C. and stirred vigorously. To the stirring mixture was added sodium triacetoxyborohydride (2.62 g, 12.4 mmol), portionwise over a period of 1 hour. The mixture was heated to 50° C. for 18 hours. The reaction was quenched with a 10% sodium bicarbonate solution and extracted with EtOAc (3×50 mL). The organic layers were combined, acidified with 1 N HCl, and extracted with DCM (8×150 mL). In a 500 mL Erlenmeyer flask, the aqueous layer was neutralized slowly with solid sodium carbonate under continuous stirring until pH ˜7-8 and then extracted with DCM (3×200 mL). The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated to afford the ethyl 1-{[4-cyano-4-(4-methylpyridin-2-yl)piperidin-1-yl]methyl}-4-oxo-4H-quinolizine-3-carboxylate that gave a proton NMR spectrum consistent with theory and a mass spectrum (ES+) m/z of 431.0 calculated for M+H+: 1H NMR (400 MHz, CDCl3) δ 9.51 (d, J=7.1 Hz, 1H), 8.43 (d, J=4.95 Hz, 1H), 8.32 (s, 1H), 8.14 (d, J=8.9 Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.43 (s, 1H), 7.26 (m, 1H), 7.06 (d, J=4.9 Hz, 1H), 4.44 (q, J=7.1 Hz, 2H), 3.75 (s, 2H), 3.01 (d, J=12.0 Hz, 2H), 2.56 (t, J=11.3 Hz, 2H), 2.39 (s, 3H), 2.29 (t, J=12.9 Hz, 2H), 2.05 (d, J=12.4 Hz, 2H), 1.44 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureThe mixture was heated to 50° C. for 18 hours
  2. customThe reaction was quenched with a 10% sodium bicarbonate solution
  3. extractionextracted with EtOAc (3×50 mL)
  4. extractionextracted with DCM (8×150 mL)
  5. stirringunder continuous stirring until pH ˜7-8
  6. extractionextracted with DCM (3×200 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-172efcee5fb648e7bcc8087a10464d29
Source dataset
uspto-grants-2012_09
Patent number
US08258135B2

Reaction notes

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