Sodium hydride → trans-Methyl 2-[6-(trifluoromethyl)pyridin-3-yl]cyclopropanecarboxylate

HRID 572018Notes

Reaction equation

HRID 572018 reaction equation
[H-].[Na+].[F:3][C:4]([F:18])([F:17])[C:5]1[N:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1.CO.[CH2:21](Cl)Cl>CS(C)=O>[F:18][C:4]([F:17])([F:3])[C:5]1[N:10]=[CH:9][C:8]([C@@H:11]2[CH2:21][C@H:12]2[C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21226129Dichloromethane methanolHCID 23402327Methyl (2E)-3-[6-(trifluoromethyl)pyridin-3-YL]prop-2-enoate

Product 1

HCID 66691074trans-Methyl 2-[6-(trifluoromethyl)pyridin-3-yl]cyclopropanecarboxylateYield 10%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a vigorously stirring mixture of NaH (31.0 mg, 1.16 mmol) in DMSO (5 mL) at ambient temperature under an argon (g) atmosphere was added (CH3)3S(I)O (248 mg, 1.12 mmol) in small portions over ca. 1 min. Following complete addition, the reaction was stirred for 20 min. A DMSO (1 mL) solution of 26A (200 mg, 0.870 mmol) was added dropwise over ca. 1 min. The reaction was left to stir for 5 h then quenched with H2O (25 mL) and extracted into EtOAc (3×30 mL). The combined organics were washed with H2O (1×15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was subjected to flash chromatography (SiO2-12 g; gradient elution: 0.25% MeOH/DCM for 3 min then 0.25-4% MeOH/DCM over 14 min at 25 mL/min) to afford 22.0 mg 26B (10% yield). m/z (ES+) M+1=246.1; HPLC tR=1.09 min. 1H NMR (500 MHz, CDCl3) δ 8.54 (d, J=1.8 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.55-7.46 (m, 1H), 3.75 (s, 3H), 2.60 (ddd, J=9.6, 6.1, 4.1 Hz, 1H), 2.00 (ddd, J=8.6, 5.6, 4.1 Hz, 1H), 1.73 (dt, J=9.2, 5.1 Hz, 1H), 1.38 (ddd, J=8.6, 6.4, 5.1 Hz, 1H).

Workup

  1. additionaddition
  2. stirringthe reaction was stirred for 20 min
  3. waitThe reaction was left
  4. stirringto stir for 5 h
  5. customthen quenched with H2O (25 mL)
  6. extractionextracted into EtOAc (3×30 mL)
  7. washThe combined organics were washed with H2O (1×15 mL), brine (15 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. washgradient elution

Sources & evidence

ORD record
ord-c9ca650c27bb4896a823142340e03dc4
Source dataset
uspto-grants-2015_05
Patent number
US09029381B2

Reaction notes

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