Sodium hydride → (1,6-Dihydro-6-oxopyridin-2-yl)methyl 4-fluorobenzoate

HRID 2400217Notes

Reaction equation

HRID 2400217 reaction equation
[OH:1][CH2:2][C:3]1[NH:8][C:7](=[O:9])[CH:6]=[CH:5][CH:4]=1.[H-].[Na+].[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1>C1COCC1>[F:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([O:1][CH2:2][C:3]2[NH:8][C:7](=[O:9])[CH:6]=[CH:5][CH:4]=2)=[O:18])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 678794-Fluorobenzoyl chlorideHCID 224765516-(Hydroxymethyl)pyridin-2-ol

Product 1

HCID 67180054(1,6-Dihydro-6-oxopyridin-2-yl)methyl 4-fluorobenzoateYield 32.48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In Example 5, 0.2006 grams (1.60 mmole) of 6-(hydroxymethyl)pyridine-2(1H)-one was suspended in 160 mL of THF in a 250 mL round bottom flask under the presence of argon gas. Then, 0.0671 g (1.68 mmole) of 60% NaH dispersed in mineral oil was added and the solution was stirred for 20 min. 0.19 mL (1.58 mmole) of 4-fluorobenzoyl chloride was dissolved in 20 mL of THF and added dropwise into the alcohol reaction mixture at a rate of 10 μL/min. The reaction stirred for 48 hours under the presence of argon gas before being quenched with 20 mL of water. The reaction was washed with ethyl acetate (4×20 mL), the organic layers combined, washed with saturated NaHCO3 (4×20 mL), washed with Brine (3×20 mL) and finally dried over MgSO4. The solvent was removed in vacuo to produce a dull yellow solid. The compound was purified by column chromatography(methanol/dichloromethane). The result was a fine white powder. (0.1287 grams, 32.48% Yield). 1H NMR (DMSO-d6, 500 MHz) δ: 5.12 (s, 2H) 6.29-6.41 (m, 2H) 7.38 (t, 2H) 7.45 (t, 1H) 8.08 (t, 2H) 11.74 (s, 1H).

Workup

  1. additionwas added
  2. stirringThe reaction stirred for 48 hours under the presence of argon gas
  3. custombefore being quenched with 20 mL of water
  4. washThe reaction was washed with ethyl acetate (4×20 mL)
  5. washwashed with saturated NaHCO3 (4×20 mL)
  6. washwashed with Brine (3×20 mL)
  7. dry with materialfinally dried over MgSO4
  8. customThe solvent was removed in vacuo
  9. customto produce a dull yellow solid
  10. customThe compound was purified by column chromatography(methanol/dichloromethane)

Sources & evidence

ORD record
ord-05223960ed034c7987fa31c76ee1c34f
Source dataset
uspto-grants-2014_08
Patent number
US08795630B2

Reaction notes

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