Potassium Carbonate → HCID 68109313, compound

HRID 2179310Notes

Reaction equation

HRID 2179310 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([O:9]N)=[CH:5][CH:4]=1.O=[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(O)(=O)C.S(=O)(=O)(O)O.O>[Br:2][C:3]1[CH:8]=[CH:7][C:6]2[O:9][C:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][C:13]=3[C:5]=2[CH:4]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 67132126O-(4-bromophenyl)hydroxylamine hydrochloride

Product 1

HCID 68109313HCID 68109313, compoundYield 40.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

The product of step A (13.7 g, 61.02 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (13.37 g, 67.12 mmol) in acetic acid (36 mL) and concentrated sulfuric acid (4 mL) were heated to 110° C. for 2 h. After concentrating in vacuo the reaction mixture was diluted with dichloromethane (100 mL) and water (200 mL), basified with saturated aqueous potassium carbonate solution at 0° C. and extracted with dichloromethane. The organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in 2-propanol (102 mL) and water (120 mL) before addition of potassium carbonate (9.5 g, 68.95 mmol) and di-tert-butyl dicarbonate (15 g, 68.9 mmol). The reaction mixture was stirred at 0° C. for 2 h then diluted with water (200 mL) and extracted three times with dichloromethane. The organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 90:10 hexane/ethyl acetate) to give tert-butyl 8-bromo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (8.7 g, 40%) as a light-pink solid: 1H NMR (CDCl3, 300 MHz) δ 7.53 (d, J=1.2 Hz, 1H), 7.36-7.25 (m, 2H), 4.51 (s, 2H), 3.82 (t, J=5.4 Hz, 2H), 2.84 (t, J=5.4 Hz, 2H), 1.50 (s, 9H).

Workup

  1. concentrationAfter concentrating in vacuo the reaction mixture
  2. additionwas diluted with dichloromethane (100 mL) and water (200 mL)
  3. custombasified with saturated aqueous potassium carbonate solution at 0° C.
  4. extractionextracted with dichloromethane
  5. dry with materialThe organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in 2-propanol (102 mL)
  9. extractionextracted three times with dichloromethane
  10. dry with materialThe organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash column chromatography (SiO2, 90:10 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-85bd4399cf444985a3e58ca319942563
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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