Dimethyl Carbonate → 3-(1-methylpyrrolidin-2-yl)-4H-pyridine-1-carboxylic acid methyl ester

HRID 901304Notes

Reaction equation

HRID 901304 reaction equation
[C:1](=[O:6])(OC)[O:2][CH3:3].[CH3:7][N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:18]([Si](C)(C)C)[CH:17]=[CH:16][N:15]([Si](C)(C)C)[CH:14]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:3][O:2][C:1]([N:15]1[CH:16]=[CH:17][CH2:18][C:13]([CH:9]2[CH2:10][CH2:11][CH2:12][N:8]2[CH3:7])=[CH:14]1)=[O:6]

Participants

5

Reactant 3

HCID 12021Dimethyl CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 219018773-(1-Methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine

Product 1

HCID 235967383-(1-methylpyrrolidin-2-yl)-4H-pyridine-1-carboxylic acid methyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethyl carbonate (0.05 mL, 0.6 mmol) in 2 mL of dry THF was slowly added 3-(1-methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine I (0.2 mL, 0.68 mmol). A solution of TBAF in THF (0.06 mL, 0.06 mmol) was then introduced dropwise and the reaction mixture was stirred at RT for 1 h. The reaction was quenched with a saturated aqueous solution of NaHCO3. The aqueous layer was extracted with ether (2 times), and the combined organic layers were washed with brine and dried over K2CO3. The solvent was removed under reduced pressure and the crude material was purified by RPLC hexanes) to afford 0.1374 g (91%) of 3-(1-methylpyrrolidin-2-yl)-4H-pyridine-1-carboxylic acid methyl ester II as a clear oil. IR (thin film, neat, NaCl): 2949, 2826, 2764, 1721, 1695, 1437, 1334, 1313, 1194, 983 cm−1. 1 HNMR (300 MHz, CDCl3): δ 6.68-6.51 (m, 2 H), 4.88-4.77 (m, 1 H), 3.65 (s, 3 H), 2.95-2.91 (m, 1 H), 2.64-2.62 (m, 2 H), 2.41-2.33 (m, 1 H), 2.05-1.93 (m, 5 H), 1.68-1.53 (m, 4 H); 13C NMR (CDCl3, 75 MHz) δ 151.81, 123.15, 122.74, 120.28, 119.63, 118.08, 117.71, 106.22, 105.94, 70.37, 56.60, 53.05, 40.16, 40.08, 28.76, 28.38, 22.37, 21.56, 21.05. HRMS Calcd for C12H18N2O2: 223.1447 [M+H]+. Found: 223.1434 [M+H]+. [α]24D−65.5 (c =8, CH2Cl2).

Workup

  1. customThe reaction was quenched with a saturated aqueous solution of NaHCO3
  2. extractionThe aqueous layer was extracted with ether (2 times)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over K2CO3
  5. customThe solvent was removed under reduced pressure
  6. customthe crude material was purified by RPLC hexanes)

Sources & evidence

ORD record
ord-24b2c630c2084ba5ace6470b7ef42757
Source dataset
uspto-grants-2008_04
Patent number
US07361768B2

Reaction notes

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