Propylene Oxide → HCID 68108948, compound

HRID 2179391Notes

Reaction equation

HRID 2179391 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](I)[C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=1.C([Mg]Br)(C)C.[CH3:28][CH:29]1[CH2:31][O:30]1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH2:28][CH:29]([OH:30])[CH3:31])[C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 6378Propylene OxideHCID 68109080HCID 68109080, compoundHCID 178418365HCID 178418365, compound

Product 1

HCID 68108948HCID 68108948, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of tert-butyl 8-bromo-6-iodo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (200 mg, 0.42 mmol) in anhydrous THF (2 mL) at −78° C. was added isopropylmagnesium bromide (2 M solution in THF, 0.4 mL, 0.84 mmol). The reaction mixture was stirred at −40° C. for 1 h and Cu(I) iodide (96 mg, 0.50 mmol) was added. The reaction mixture was stirred at −40° C. for a further 30 min then 2-methyloxirane (0.29 mL, 4.18 mmol) was added. After 1 h, the reaction was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic extract was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 7:3 hexanes/ethyl acetate) to give tert-butyl 8-bromo-6-(2-hydroxypropyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (110 mg, 17%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.42 (d, J=1.5 Hz, 1H), 7.22 (d, J=1.5 Hz, 1H), 4.50 (s, 2H), 4.30-4.16 (m, 1H), 3.82 (br s, 2H), 3.05-2.91 (m, 2H), 2.85 (br s, 2H), 1.50 (s, 9H), 1.27 (d, J=6.3 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred at −40° C. for a further 30 min
  2. waitAfter 1 h
  3. customthe reaction was quenched with saturated ammonium chloride
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. dry with materialwas dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (SiO2, 7:3 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-5a2f50b28df846ffbe4e29b779f6e591
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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