1,1-Dibromoethane → HCID 66727983, compound

HRID 1961532Notes

Reaction equation

HRID 1961532 reaction equation
[Cl-].[Ce+3].[Cl-].[Cl-].[CH2:5]([O:7][CH:8]([O:16][CH2:17][CH3:18])[C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[CH3:6].[Mg].BrC(Br)C.[C:24]([O:28][C:29]([N:31]1[CH2:34][CH2:33][C:32]1=O)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(OC(C)(C)C)=[O:37]>O1CCCC1>[CH2:5]([O:7][CH:8]([O:16][CH2:17][CH3:18])[C:9]1[CH:14]=[CH:13][C:12]([C:33]2([OH:37])[CH2:34][N:31]([C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])[CH2:32]2)=[CH:11][CH:10]=1)[CH3:6]

Participants

8

Reactant 6

HCID 112011,1-DibromoethaneHCID 24636Cerium(III) chlorideHCID 61207tert-Butyl FormateHCID 6883401-Bromo-4-(diethoxymethyl)benzeneHCID 5462224Magnesium2×HCID 23179885tert-Butyl 2-oxoazetidine-1-carboxylate

Product 1

HCID 66727983HCID 66727983, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
65 °C

Procedure

Cerium chloride (71.4 g, 290 mmoles) was slurried in tetrahydrofuran (600 mL) and heated to 65° C. for 2.5 hours, then cooled to room temperature In a separate flask, 4-bromobenzaldehyde diethylacetal (100 g, 386 mmoles) was dissolved in tetrahydrofuran (750 mL). Magnesium turnings (5.9 g, 241 mmoles) and dibromoethane (0.5 mL) were added and the mixture heated to reflux for 2.5 hours, until all the magnesium had reacted. Heating was removed and the Grignard solution cooled in an ice bath. The cerium chloride/tetrahydrofuran slurry was cooled in an ice bath to 0° C. The Grignard solution was added, portionwise, and the mixture stirred at 0° C. for 45 minutes. N-(t-butoxycarbonyl)azetidinone (41.3 g, 241 mmoles) dissolved in tetrahydrofuran (200 mL) was added portionwise and the reaction allowed to stir at 0° C. for 30 minutes. The reaction was quenched with saturated sodium carbonate solution (500 mL) and then diluted with ethyl acetate (2000 mL). The organic phase was washed with water (3×500 mL), separated, dried over anhydrous magnesium sulphate, filtered and evaporated to dryness to give a yellow oil weighing 120 g which was purified using normal phase chromatography (600 g SiO2 column, loaded as a solution in 25 mL of dichloromethane, linear gradient of 10% tert-butylmethylether in n-heptane to 100% tert-butylmethylether over 60 minutes, 150 mL/minutes, 55 mL fractions using the ‘Threshold OR Slope’ method) to give a light yellow oil weighing 65 g, which NMR suggests is the desired acetal product. 1HNMR (CDCl3) δ ppm: 7.50 (4H), 5.50 (1H), 4.15 (2H), 4.30 (2H), 3.55 (4H), 1.50 (9H), 1.25 (6H); m/z (ESI) 252 [M+H-Boc]+.

Workup

  1. temperaturecooled to room temperature In a separate flask
  2. temperaturethe mixture heated
  3. customhad reacted
  4. temperatureHeating
  5. customwas removed
  6. temperaturethe Grignard solution cooled in an ice bath
  7. temperatureThe cerium chloride/tetrahydrofuran slurry was cooled in an ice bath to 0° C
  8. additionThe Grignard solution was added
  9. additionwas added portionwise
  10. stirringto stir at 0° C. for 30 minutes
  11. customThe reaction was quenched with saturated sodium carbonate solution (500 mL)
  12. additiondiluted with ethyl acetate (2000 mL)
  13. washThe organic phase was washed with water (3×500 mL)
  14. customseparated
  15. dry with materialdried over anhydrous magnesium sulphate
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customto give a yellow oil
  19. customwas purified
  20. waitlinear gradient of 10% tert-butylmethylether in n-heptane to 100% tert-butylmethylether over 60 minutes
  21. customto give a light yellow oil

Sources & evidence

ORD record
ord-bb1cf6970c664e9c87aed8f663dfa7ad
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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