Methyl formate → 1-(1-Benzylpiperidin-4-yl)-2-formyl-3-phenyl-1-propanone

HRID 1068130Notes

Reaction equation

HRID 1068130 reaction equation
[O:1]([C:3](C)(C)C)[K].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20](=[O:29])[CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(OC)=O>C1COCC1>[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20](=[O:29])[CH:21]([CH:3]=[O:1])[CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 7865Methyl formateHCID 211930001-(1-Benzylpiperidin-4-yl)-3-phenyl-1-propanoneHCID 178418922HCID 178418922, compound

Product 1

HCID 211930731-(1-Benzylpiperidin-4-yl)-2-formyl-3-phenyl-1-propanoneYield 130.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Into a 100 mL 3-neck round-bottom flask was weighed 0.336 g KO-t-Bu and 4 mL anhydrous THF was added. The mixture was cooled with an ice bath under nitrogen, and to it was added a solution of 0.29 g 1-(1-benzylpiperidin-4-yl)-3-phenyl-1-propanone from the last step and 1.80 g methyl formate in 12 mL THF over 5 minute with stirring. After stirring for an additional 15 min, the cooling bath was removed, and the yellowish cloudy mixture was stirred for 2 hours. The mixture was then poured into water, extracted with 4×50 mL ether, 40 mL dichloromethane, and 3×40 mL THF and the combined organic layers were washed with 50 mL each of water and saturated brine, dried over Na2SO4, and concentrated under reduced pressure to give 0.414 g of the title compound as a sticky yellowish solid. This crude product was used without further purification in the next step. RF: 0.59 (EtOAc with 3% (v/v) Et3N and 5% (v/v) MeOH). 1H NMR (500 MHz, DMSO-d6): δ7.97 (s, 1H), 7.20˜7.30 (m, 5H), 7.14˜7.17 (m, 2H), 7.04˜7.09 (m, 3H), 6.85 (s, 1H), 3.45 (s, ˜2H), 2.81˜2.89 (m, 1H), 2.76˜2.80 (m, 2H), 1.97˜2.03 (m, 2H), 1.46˜1.56 (m, 4H). The Ph—CH2—C═ signal was not observed, possibly overlapping with the large water signal. ESI-MS 336.1 (M+H), HPLC A: 2.32 min.

Workup

  1. customInto a 100 mL 3-neck round-bottom flask was weighed
  2. temperatureThe mixture was cooled with an ice bath under nitrogen
  3. stirringAfter stirring for an additional 15 min
  4. customthe cooling bath was removed
  5. stirringthe yellowish cloudy mixture was stirred for 2 hours
  6. additionThe mixture was then poured into water
  7. extractionextracted with 4×50 mL ether, 40 mL dichloromethane, and 3×40 mL THF
  8. washthe combined organic layers were washed with 50 mL each of water and saturated brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d891daef4d564d33b67f43c589ec5173
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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