Ammonium Hydroxide → 5-Benzyloxy-2-difluoromethyl-1H-pyridin-4-one

HRID 1187467Notes

Reaction equation

HRID 1187467 reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:17])[F:16])O[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[NH4+:20].C(Cl)Cl.CCOC(C)=O>C(O)C>[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:17])[F:16])[NH:20][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 21226138Dichloromethane ethylacetateHCID 598182925-Benzyloxy-2-difluoromethyl-pyran-4-one

Product 1

HCID 672821655-Benzyloxy-2-difluoromethyl-1H-pyridin-4-oneYield 74%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-Benzyloxy-2-difluoromethyl-pyran-4-one (0.47 g, 1.9 mmol) was dissolved in ethanol (15 mL) to give a slightly yellow clear solution. Ammonium hydroxide (28-30% aqueous solution, 15 mL, 235 mmol) was added at room temperature. The resulting solution was stirred at ambient temperature for 24 hours. The progress of the reaction was monitored by TLC (CH2Cl2/EtOAc, 7/3, v/v) and HPLC Method 2. Volatiles were removed in vacuo and the residue was purified by column chromatography on silica (95/5 then 85/15 CH2Cl2/MeOH, v/v) to give the title compound as a light yellow solid (0.35 g, 74%) with a HPLC purity (peak percent area) of 98.2%. 1H NMR (300 MHz, DMSO-D6) (ppm): 10.99 (br. s, 1H), 8.22 (s, 1H), 7.32-7.32 (m, 5H), 7.06 (s, 1H), 6.75 (t, J=55.4 Hz, 1H), 5.23 (s, 2H); MS (m/z) 252 [M+1]+, 192.2, 91.3 (100%).

Workup

  1. customto give a slightly yellow clear solution
  2. customVolatiles were removed in vacuo
  3. customthe residue was purified by column chromatography on silica (95/5

Sources & evidence

ORD record
ord-d7cab18beb574ad9958f98478ef2ef47
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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