Water → HCID 66749560, compound

HRID 2402120Notes

Reaction equation

HRID 2402120 reaction equation
Br[CH2:2][C:3]1[N:4]=[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[S:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[O:19]1[C:24]2[CH:25]=[CH:26][C:27](B(O)O)=[CH:28][C:23]=2[O:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:19]1[C:24]2[CH:25]=[CH:26][C:27]([CH2:2][C:3]3[N:4]=[C:5]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[S:6][C:7]=3[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:28][C:23]=2[O:22][CH2:21][CH2:20]1

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2776178(2,3-Dihydro-1,4-benzodioxin-6-yl)boronic acidHCID 66749126HCID 66749126, compound

Product 1

HCID 66749560HCID 66749560, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

Ethyl 4-(bromomethyl)-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (109.4 mg, 0.326 mmol), 1,4-benzodioxane-6-boronic acid (91.0 mg, 0.506 mmol), tetrakis(triphenylphosphine)palladium(0) (43.0 mg, 0.0372 mmol), cesium carbonate (430 mg, 1.3 mmol), 1,4-dioxane (2.19 mL, 28.0 mmol) and water (43.8 uL, 2.43 mmol) were combined in a vial equipped with a stirbar. The vial was sealed and the atmosphere was replaced with nitrogen. The vial was sonicated for 1 minute then heated at 90° C. (heating block temperature) with stirring for 1 hour. The reaction was cooled to room temperature, the vial was opened and the contents were quenched into stirring saline. The quench mixture was transferred to a separatory funnel and extracted twice with ethyl acetate. The extracts were combined, washed with saline, dried over sodium sulfate, filtered, and concentrated in vacuo to leave an orange oil. The crude residue was purified by silica gel chromatography (gradient elution: ethyl acetate/hexane from 0/100 to 100/0) to give ethyl 4-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (60 mg, 47% yield) as a white powder. LC/MS (FA) ES+ 391; 1H NMR (300 MHz, DMSO-d6) δ: 6.67-6.74 (m, 3H), 4.20 (q, 2H, J=7.1 Hz), 4.17 (s, 4H), 4.07 (s, 2H), 3.69-3.65 (m, 4H), 3.46-3.43 (m, 4H), 1.24 (t, 3H, J=7.1 Hz).

Workup

  1. customa vial equipped with a stirbar
  2. customThe vial was sealed
  3. customThe vial was sonicated for 1 minute
  4. temperature(heating block temperature)
  5. temperatureThe reaction was cooled to room temperature
  6. customthe contents were quenched
  7. stirringinto stirring saline
  8. customThe quench mixture was transferred to a separatory funnel
  9. extractionextracted twice with ethyl acetate
  10. washwashed with saline
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto leave an orange oil
  15. customThe crude residue was purified by silica gel chromatography (gradient elution: ethyl acetate/hexane from 0/100 to 100/0)

Sources & evidence

ORD record
ord-f4054809c09544aabe31d3e338efba69
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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