Benzaldehyde → (S)-3-benzyl-5-(1-methylpyrrolidin-2-yl)-pyridine

HRID 901303Notes

Reaction equation

HRID 901303 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][N:10]1[CH2:14][CH2:13][CH2:12][CH:11]1[C:15]1[CH:20]([Si](C)(C)C)[CH:19]=[CH:18][N:17]([Si](C)(C)C)[CH:16]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1>[CH2:1]([C:19]1[CH:18]=[N:17][CH:16]=[C:15]([C@@H:11]2[CH2:12][CH2:13][CH2:14][N:10]2[CH3:9])[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 219018773-(1-Methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine

Product 1

HCID 11594026(S)-3-benzyl-5-(1-methylpyrrolidin-2-yl)-pyridineYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of benzaldehyde (0.07 mL, 0.75 mmol) in freshly distilled THF was added dropwise 3-(1-methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine i (0.21 g, 0.68 mmol). A degassed solution of TBAF in THF (1 M) stored over molecular sieves was slowly added to the mixture. The reaction mixture was stirred under Ar at RT for one day. It was then poured into a saturated aqueous solution of NaHCO3. The product was extracted with diethyl ether (2 times). The combined organic layers were washed with brine and dried over MgSO4. The solvent was evaporated under reduced pressure and the residue was purified by RPLC (silica gel, 10% MeOH/EtOAc) to give 31% (0.0525 g) of (S)-3-benzyl-5-(1-methylpyrrolidin-2-yl)-pyridine iv as a clear oil. IR (thin film, neat, NaCl): 3236, 2954, 2778, 1666, 1613, 1449, 1037 cm−1. 1H NMR (400 MHz, CDCl3) δ 8.40-8.34 (m, 2 H), 7.88 (dd, 1 H, J=1.6 and 13.2 Hz), 7.37-7.24 (m, 4 H), 5.84 (s, 1 H), 3.13-3.02 (m, 2 H), 2.25-1.69 (m, 10 H); 13C NMR (75 MHz, CDCl3) δ 148.43, 147.42, 143.90, 140.11, 138.19, 133.30, 133.25, 128.82, 127.95, 126.81, 74.24, 74.03, 69.15, 57.04, 40.47, 35.10, 22.51. HRMS Calcd for C17H20N2: 252.1626 [M+H]+. Found: 252.1635 [M+H]+. [α]25D−26 (CH2Cl2, c=1.51).

Workup

  1. additionwas slowly added to the mixture
  2. extractionThe product was extracted with diethyl ether (2 times)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by RPLC (silica gel, 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-1f79d3800edc4ef29e415034877892bf
Source dataset
uspto-grants-2008_04
Patent number
US07361768B2

Reaction notes

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