4-Bromoanisole → HCID 130369142, compound

HRID 1873926Notes

Reaction equation

HRID 1873926 reaction equation
Br[CH2:2][CH2:3]Br.[Mg].Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[CH3:15][C:16]1([CH3:30])[O:20][CH2:19][C@@H:18]([CH:21]=[O:22])[N:17]1[C:23]([O:25][C:26](C)(C)C)=[O:24].[CH2:31]1[CH2:35]O[CH2:33][CH2:32]1>S(C)C.[Cu]I>[OH:22][C@H:21]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[C@H:18]1[CH2:19][O:20][C:16]([CH3:30])([CH3:15])[N:17]1[C:23]([O:25][CH2:26][C:3]1[CH:2]=[CH:33][CH:32]=[CH:31][CH:35]=1)=[O:24]

Participants

8

Reactant 5

HCID 77304-BromoanisoleHCID 78391,2-DibromoethaneHCID 8028Tetrahydrofuran4×HCID 1798243-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (S)-(-)-HCID 5462224Magnesium

Product 1

HCID 130369142HCID 130369142, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1068Dimethyl SulfideSolvent

Procedure

1,2-dibromoethane (0.2 mL) was added slowly to a hot (65° C.) solution of magnesium turnings (0.91 g, 37 mmol) in THF (14 mL), followed by the dropwise addition of a solution of 4-bromo anisole (4 mL, 32 mmol) in THF (14 mL). The mixture was refluxed for 2 hours and then cooled to room temperature. The grignard solution was added dropwise to a suspension of CuI (6.8 g, 36 mmol) in a mixture of Me2S (20 mL)/THF (100 mL) at −78° C. The mixture was warmed slowly to −45° C. and stirred for 30 min keeping the temperature between −45 to −35° C. The mixture was cooled back to −78° C., and a solution of the Garner's aldehyde [(R)-benzyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate](3.20 g, 12.6 mmol) in THF (15 mL) was added dropwise. The mixture was stirred at low temperature overnight (15 h, T max=10° C.). The reaction mixture was quenched with NH4Cl (sat. 100 mL) and extracted with EtOAc (50 mL). The solvent was removed to dryness and the mixture was purified by column chromatography (SiO2, using a mixture of hexane/EtOAc/acetone) and the product was obtained as a colorless oil (1.697 g, 36% yield).

Workup

  1. temperatureThe mixture was refluxed for 2 hours
  2. temperatureThe mixture was warmed slowly to −45° C.
  3. custombetween −45 to −35° C
  4. temperatureThe mixture was cooled back to −78° C.
  5. stirringThe mixture was stirred at low temperature overnight (15 h, T max=10° C.)
  6. customThe reaction mixture was quenched with NH4Cl (sat. 100 mL)
  7. extractionextracted with EtOAc (50 mL)
  8. customThe solvent was removed to dryness
  9. customthe mixture was purified by column chromatography (SiO2
  10. additiona mixture of hexane/EtOAc/acetone) and the product

Sources & evidence

ORD record
ord-604e27e9b27344c8b1c70727b40a18b1
Source dataset
uspto-grants-2012_11
Patent number
US08304447B2

Reaction notes

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