Tetrahydrofuran → HCID 23005486, compound

HRID 546370Notes

Reaction equation

HRID 546370 reaction equation
[C:1]([CH2:4][C:5](=[O:7])[CH3:6])(=[O:3])[CH3:2].[H-].[Na+].[NH4+].[Cl-].C[CH2:13][O:14][C:15]([CH3:17])=[O:16].C[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].[CH2:24]1COCC1>>[C:1]([CH:4]([C:5](=[O:7])[CH3:6])[CH2:24][C:21]1[CH:20]=[CH:19][C:17]([C:15]([O:14][CH3:13])=[O:16])=[CH:23][CH:22]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31261AcetylacetoneHCID 21226206Ethyl acetate hexane

Product 1

HCID 23005486HCID 23005486, compoundYield 86%

Conditions

Temperature
50 °C

Procedure

Acetylacetone (1.9 mL, 19 mmol) was added dropwise over 30 minutes to a cooled (ice/H2O bath) suspension of 95% NaH (0.42 g, 18 mmol) in anhydrous THF (65 mL). After H2 evolution had ceased, a solution of methyl (4-bromomethyl)benzoate (4.01 g, 17.5 mmol) in anhydrous THF (9 mL) was added at once with stirring. The reaction mixture was heated to 50° C. (internal temperature) for 48 h, cooled to room temperature, and poured into saturated aqueous NH4Cl (125 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (3×100 mL). The combined organic extracts were dried (Na2SO4). The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give an oily residue. Flash column chromatography (EtOAc:hexane (1:8)) gave 4e as a pale oil (3.78 g, 86%). 1H NMR (300 MHz, CDCl3): δ 7.95 (d, J=8.1 Hz, 2H, enol), 7.92 (d, J=8.1 Hz, 2H, keto), 7.21 (d, J=8.1 Hz, 2H, keto), 7.20 (d, J=8.1 Hz, 2H, enol), 4.00 (t, J=7.5 Hz, 1H, keto), 3.88 (s, 3H, enol), 3.87 (s, 3H, keto), 3.67 (s, 2H, enol), 3.17 (d, J=7.5 Hz, 2H, keto), 2.11 (s, 6H, keto), 2.03 (s, 6H, enol). 13C NMR (75 MHz, CDCl3): δ 203.2, 192.1, 167.1, 145.4, 143.7, 130.2, 128.9, 128.7, 127.7, 107.9, 69.7, 34.2, 33.3, 29.9, 23.5. IR (thin film, CHCl3 cm−1): 3420, 3002, 2953, 2844, 1935, 1732, 1710, 1609, 1346, 1359, 1272, 1178, 1109, 1019. MS (ESI): m/z 271 (M+Na). Anal. Calcd. for C14H16O4: C, 67.73; H, 6.50; O, 25.78. Found: C, 67.69; H, 6.48; O, 25.81.

Workup

  1. temperaturea cooled
  2. temperaturecooled to room temperature
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×100 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. customThe drying agent was removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customto give an oily residue

Sources & evidence

ORD record
ord-18f55327697f47c6970c2213f4c91dce
Source dataset
uspto-grants-2011_05
Patent number
US07935847B2

Reaction notes

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