Dimethylformamide → tert-Butyl 3-(4-cyanophenyl)-3-hydroxyazetidine-1-carboxylate

HRID 1487904Notes

Reaction equation

HRID 1487904 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:19])[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:20][N:21](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:20]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:19])[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1)#[N:21]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 580797831-Boc-3-(4-bromophenyl)-3-hydroxyazetidine2×

Product 1

HCID 90066657tert-Butyl 3-(4-cyanophenyl)-3-hydroxyazetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Into a 500-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of tert-butyl 3-(4-bromophenyl)-3-hydroxyazetidine-1-carboxylate (compound 43.1, 16.3 g, 49.7 mmol) in N,N-dimethylformamide (250 mL), zinc cyanide (8.7 g, 75 mmol) and Pd(PPh3)4 (5.77 g, 5.00 mmol). The resulting mixture was stirred for 15 h at 100° C., then cooled to room temperature. The reaction was quenched with saturated aqueous FeSO4 (500 mL) and stirred vigorously. The mixture was filtered through Celite® and the layers from the filtrate were separated. The aqueous phase was extracted with ethyl acetate (300 mL) and the combined organic layers were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/100-1/3) as the eluent to yield 14 g (crude) of the title compound as a white solid.

Workup

  1. customInto a 500-mL round-bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturecooled to room temperature
  4. customThe reaction was quenched with saturated aqueous FeSO4 (500 mL)
  5. stirringstirred vigorously
  6. filtrationThe mixture was filtered through Celite®
  7. customthe layers from the filtrate were separated
  8. extractionThe aqueous phase was extracted with ethyl acetate (300 mL)
  9. washthe combined organic layers were washed with brine (2×100 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/100-1/3) as the eluent

Sources & evidence

ORD record
ord-512fcf22e09a413b93062b9050a1e19c
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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