Tetrahydrofuran → HCID 66747748, compound

HRID 2402096Notes

Reaction equation

HRID 2402096 reaction equation
[H-].[Na+].[C:3](=[O:8])([O:6][CH3:7])OC.[Cl:9][C:10]1[CH:30]=[CH:29][C:13]([CH2:14][C:15]2[N:16]=[C:17]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[S:18][C:19]=2[C:20](=[O:22])[CH3:21])=[CH:12][CH:11]=1.[CH2:31]1COCC1>>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][C:15]2[N:16]=[C:17]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[S:18][C:19]=2[C:20](=[O:22])[CH2:21][C:3]([O:6][CH2:7][CH3:31])=[O:8])=[CH:29][CH:30]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 66747676HCID 66747676, compound

Product 1

HCID 66747748HCID 66747748, compoundYield 25%

Procedure

To a flask containing 60% NaH in mineral oil (213 mg, 5.32 mmol) under nitrogen was added THF (31.7 mL) and carbonic acid, dimethyl ester (0.448 mL, 5.32 mmol). The mixture was heated to 60 degrees and a solution of 1-(4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazol-5-yl)ethanone (875 mg, 2.66 mmol) in THF (12.7 mL) was then added. The mixture was heated at 60 degrees for 1 hour. The reaction was cooled and quenched with methanol (5 mL), then saturated NH4Cl (10 mL). The organic solvents were concentrated in vacuo, and the aqueous residue was diluted with water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined organic layers were dried, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (EA/DCM=0/100→40/60) to give 253 mg (25% yield) of the title compound. as an oil. LC/MS (FA) ES+ 387, 389. 1H NMR (300 MHz, CDCl3) δ: 8.76-8.74 (m, 2H), 7.83-7.81 (m, 2H), 7.35-7.32 (m, 2H), 7.26-7.23 (m, 2H), 4.53 (s, 2H), 3.89 (s, 2H), 3.77 (s, 3H).

Workup

  1. temperatureThe mixture was heated to 60 degrees
  2. temperatureThe mixture was heated at 60 degrees for 1 hour
  3. temperatureThe reaction was cooled
  4. customquenched with methanol (5 mL)
  5. concentrationThe organic solvents were concentrated in vacuo
  6. additionthe aqueous residue was diluted with water (10 mL)
  7. extractionextracted with ethyl acetate (2×20 mL)
  8. customThe combined organic layers were dried
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel chromatography (EA/DCM=0/100→40/60)

Sources & evidence

ORD record
ord-7c646fda69e04b2aabd90f69be08b83c
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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