Diethyl Carbonate → HCID 12971970, compound

HRID 1068046Notes

Reaction equation

HRID 1068046 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][C:3]=1[C:15](=[O:17])[CH3:16].[H-].[Na+].[C:20](=O)([O:24]CC)[O:21][CH2:22][CH3:23]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[CH:4][C:3]=1[C:15](=[O:17])[CH2:16][C:20]([O:21][CH2:22][CH3:23])=[O:24]

Participants

4

Reactant 3

HCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 9856131HCID 9856131, compound

Product 1

HCID 12971970HCID 12971970, compoundYield 79%

Conditions

Temperature
0 °C

Procedure

A solution of 1-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-1-ethanone (19.6 g) of Preparation No. 54 in diethyl carbonate (150 mL) is cooled to 0° C., and sodium hydride (60% dispersion, 6.6 g) is added slowly to the reaction mixture. The reaction is stirred at 0° C. for 3 hours, and then is allowed to warm to room temperature overnight. The reaction mixture is quenched with acetic acid (10 mL), diluted with water (200 mL) and then basified with sat. sodium carbonate. The solution is then extracted with ether (3×200 mL). The combined organic layers are washed with sat. sodium bicarbonate (100 mL) and brine (50 mL). The combined aqueous layers are back-extracted with ether (50 mL). The combined organic layers are then dried (Na2SO4) and concentrated in vacuo to an orange oil. The crude product is purified in 2 batches by column chromatography (heptane/IPA, 8/1; 4/1) to afford 20.2 g (79%) of the title compound as a yellow oil.

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe reaction mixture is quenched with acetic acid (10 mL)
  3. additiondiluted with water (200 mL)
  4. extractionThe solution is then extracted with ether (3×200 mL)
  5. washThe combined organic layers are washed with sat. sodium bicarbonate (100 mL) and brine (50 mL)
  6. extractionThe combined aqueous layers are back-extracted with ether (50 mL)
  7. dry with materialThe combined organic layers are then dried (Na2SO4)
  8. concentrationconcentrated in vacuo to an orange oil
  9. customThe crude product is purified in 2 batches by column chromatography (heptane/IPA, 8/1; 4/1)

Sources & evidence

ORD record
ord-6426d9efefbc4fc2976a95232ca4d4e0
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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