Sodium Sulfate → HCID 178519076, compound

HRID 1968001Notes

Reaction equation

HRID 1968001 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].[NH2:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[CH2:20][O:21][C:22]2=[O:27]>ClCCl>[F:1][C:2]1[CH:9]=[CH:8][C:5](/[CH:6]=[N:17]/[C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][O:21][C:22]3=[O:27])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24436Sodium SulfateHCID 680234-FluorobenzaldehydeHCID 122846494-Amino-1,3-dihydro-2-benzofuran-1-one

Product 1

HCID 178519076HCID 178519076, compoundYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 4-fluorobenzaldehyde (3 g, 20.4 mmol) and anhydrous sodium sulfate (29 g, 20.4 mmol) in anhydrous dichloromethane (200 mL) was added 4-aminoisobenzofuran-1(3H)-one (3.04 g, 24.5 mmol) at 0° C. After the addition, the mixture was stirred at room temperature for 6 days. The mixture was filtered and the cake was washed with dichloromethane (50 mL×3). The filtrate was concentrated to give crude product. The crude product was washed with petroleum ether to give (E)-4-(4-fluorobenzylideneamino)isobenzofuran-1(3H)-one (4.25 g, yield 81%); LC-MS (ESI) m/z: 256 (M+1)+. A mixture of (E)-4-(4-fluorobenzylideneamino)isobenzofuran-1(3H)-one (2.53 g, 10 mmol) and 1-methyl-1H-imidazole-2-carbaldehyde (1.21 g, 11 mmol) in ethyl propionate (50 mL) was cooled to 0° C. Then a solution of sodium ethanoxide in ethanol [sodium (1 g, 44 mmol) in ethanol (30 mL)] was added drop-wise. After the addition, the mixture was stirred at room temperature for 2 hr. The mixture was quenched with water (10 mL) and solvent was removed in vacuum. The residue was dissolved in water, and then extracted with ethyl acetate (100 mL×4). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=10:1 to 1:10) to give ethyl 2-(4-fluorophenyl)-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (210 mg, yield 5%). LC-MS (ESI) m/z: 394 (M+1)+.

Workup

  1. additionAfter the addition
  2. filtrationThe mixture was filtered
  3. washthe cake was washed with dichloromethane (50 mL×3)
  4. concentrationThe filtrate was concentrated
  5. customto give crude product
  6. washThe crude product was washed with petroleum ether

Sources & evidence

ORD record
ord-4f262bb2dc0a492db5c94fb5e017dc6a
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

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