Triethylamine → (2-Fluoropyridin-4-yl)methyl methanesulfonate

HRID 426116Notes

Reaction equation

HRID 426116 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>C(Cl)(Cl)Cl.ClCCl>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][S:18]([CH3:17])(=[O:20])=[O:19])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 11332468(2-Fluoropyridin-4-yl)methanol

Product 1

HCID 10488448(2-Fluoropyridin-4-yl)methyl methanesulfonate

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2-Fluoro-pyridin-4-yl)-methanol (37) (381 mg, 3 mmol) in chloroform (30 ml) at 0° C. (ice bath), was added triethylamine (630 μl, 4.5 mmol) followed by methanesulfonyl chloride (270 μl, 3.6 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo to provide Methanesulfonic acid 2-fluoro-pyridin-4-ylmethyl ester (38). A flask was charged with Methanesulfonic acid 2-fluoro-pyridin-4-ylmethyl ester (38) from above, 3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (32) (891 mg, 3 mmol), anhydrous powdered potassium carbonate (408 mg, 3 mmol), and lithium iodide (402 mg, 3 mmol). Anhydrous DMF (15 ml) was then added into the mixture and stirred for 5.5 hr at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through celite pad, and evaporated in vacuo to give a pale yellow foam. The crude product was purified by silica gel column chromatography (eluent, methanol:chloroform (2:98)) to afford 366 mg (30%) of Example H as a pale yellow foam, which was recrystallized from chloroform-ether to give a white solid; 1H NMR (200 MHz, CDCl3) δ: 1.12 (3H, d, J=6.8 Hz), 1.23 (3H, d, J=6.8 Hz), 2.25 (1H, m), 2.42 (3H, s), 4.66 (1H, d, J=16.7 Hz), 4.93 (1H, d, J=16.7 Hz), 6.61 (1H, s), 6.90 (1H, d, J=5.3 Hz), 7.71 (2H, s), 7.91 (1H, s), 8.04 (1H, d, J=5.3 Hz), 9.44 (1H, s); m/z (EI): 406 (M+); HRMS (EI) Calcd. 406.144104, Found 406.144119.

Workup

  1. washwashed with aqueous saturated sodium bicarbonate solution
  2. dry with materialdried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was further dried in high vacuo

Sources & evidence

ORD record
ord-bc3fc744365148948a10d329cdf1ea01
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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