Diethyl Carbonate → HCID 12971970, compound

HRID 480647Notes

Reaction equation

HRID 480647 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:17](=[O:19])[CH3:18].[C:20](=O)([O:24]CC)[O:21][CH2:22][CH3:23]>>[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)=[CH:6][C:5]=1[C:17](=[O:19])[CH2:18][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

Sodium hydride (60% dispersion in mineral oil, 6.6 g) is slowly added to a solution of 1-(2-fluoro-5-(4-morpholinylmethyl)phenyl)ethanone (Preparation 2, 19.6 g) in diethyl carbonate at 0° C. The mixture is stirred at 0° C. for 1 h and allowed to warm to rt overnight. The reaction is quenched with acetic acid (10 mL), diluted with water (200 mL) and made basic with sat. aq. Na2CO3. The mixture is extracted with diethyl ether (3×200 mL). The combined organic layers are washed with sat. NaHCO3 (100 mL) and brine (50 mL). The combined aqueous layers are back-extracted with diethyl ether (50 mL). The organic layers are combined, dried (Na2SO4) and concentrated in vacuo to an orange oil. The crude product is purified by column chromatography (heptane/IPA, 8/1; 4/1; CH2Cl2/MeOH, 98/2) to afford 20.2 g (79%) of the compound as a yellow oil. Physical characteristics: 1H NMR (300 MHz, DMSO-d6) δ 7.78, 7.65-7.60, 7.32, 4.10, 4.05, 3.57, 3.50, 2.34, 1.16; IR (liq.) 1996, 1979, 1744, 1689, 1626, 1611, 1493, 1331, 1260, 1215, 1147, 1117, 865 cm−1; MS (ESI+) m/z 310 (M+H)+. Anal. Calcd for C16H20FNO4: C, 62.12; H, 6.52; N, 4.53. Found: C, 61.96; H, 6.67; N, 4.44.

Workup

  1. temperatureto warm to rt overnight
  2. customThe reaction is quenched with acetic acid (10 mL)
  3. additiondiluted with water (200 mL)
  4. extractionThe mixture is extracted with diethyl ether (3×200 mL)
  5. washThe combined organic layers are washed with sat. NaHCO3 (100 mL) and brine (50 mL)
  6. extractionThe combined aqueous layers are back-extracted with diethyl ether (50 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo to an orange oil
  9. customThe crude product is purified by column chromatography (heptane/IPA, 8/1; 4/1; CH2Cl2/MeOH, 98/2)

Sources & evidence

ORD record
ord-268bd9d7acd74279a0f1f01dae429d02
Source dataset
uspto-grants-2003_11
Patent number
US06653307B2

Reaction notes

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