Methanesulfonic Acid → HCID 68109080, compound

HRID 2179377Notes

Reaction equation

HRID 2179377 reaction equation
CS(O)(=O)=O.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([O:13]N)=[C:9]([I:15])[CH:8]=1.O=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.CS(O)(=O)=O.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(O)(=O)C>[Br:6][C:7]1[CH:8]=[C:9]([I:15])[C:10]2[O:13][C:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C:18]=3[C:11]=2[CH:12]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 90495Di-tert-butyl dicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86667998HCID 86667998, compound

Product 1

HCID 68109080HCID 68109080, compoundYield 12.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of the product of step B (7.0 g, 17.0 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (3.73 g, 18.7 mmol) was suspended in a mixture of glacial acetic acid (63 mL) and methanesulfonic acid (7 mL). The suspension was heated to 110° C. for 3 h. After cooling to ambient temperature the reaction mixture was concentrated in vacuo, cooled to 0° C., quenched with 5% KOH solution and suspended in 2-propanol (100 mL) followed by addition of di-tert-butyl dicarbonate (4.45 g, 20.4 mmol). After stirring for 12 h, the mixture was concentrated in vacuo and extracted with dichloromethane. The organic layer was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 95:5 hexanes/ethyl acetate) to give tert-butyl 8-bromo-6-iodo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (1.0 g, 9%) as a yellow brown solid: 1H NMR (CDCl3, 300 MHz) δ 7.71 (d, J=1.8 Hz, 1H), 7.50 (br s, 1H), 4.49 (br s, 2H), 3.87-3.78 (m, 2H), 2.94-2.87 (m, 2H), 1.50 (s, 9H).

Workup

  1. temperatureAfter cooling to ambient temperature the reaction mixture
  2. concentrationwas concentrated in vacuo
  3. temperaturecooled to 0° C.
  4. customquenched with 5% KOH solution
  5. concentrationthe mixture was concentrated in vacuo
  6. extractionextracted with dichloromethane
  7. concentrationThe organic layer was concentrated in vacuo
  8. customthe residue purified by flash column chromatography (SiO2, 95:5 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7098f91e92d9477da971c628b72aceb9
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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