4-Bromoanisole → HCID 67979402, compound

HRID 528761Notes

Reaction equation

HRID 528761 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[C:15]([O:19][C:20]([N:22]1[CH2:25][CH:24]([CH:26]=[O:27])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CCCCCCC.C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:25][CH:24]([CH:26]([OH:27])[C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 77304-BromoanisoleHCID 10726182Tert-butyl 3-formylazetidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67979402HCID 67979402, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Procedure

To 2.2 g (11.8 mmol) 4-bromoanisole in 30 mL dry heptane under nitrogen was added 8.02 mL (1.6 M in hexane, 12.83 mmol) n-butyl lithium dropwise, and the mixture was stirred at room temperature for 30 minutes. The solution was then cooled to −78° C. and a solution of 2.0 g (10.7 mmol) 3-formyl-azetidine-1-carboxylic acid tert-butyl ester (route 18, step a) in 30 mL dry THF was added. The resultant mixture was allowed to warm to room temperature, quenched with 50 mL 1 M sodium bicarbonate and extracted with DCM (2×50 mL). The combined organic layers were dried over Na2SO4. After filtration and evaporation of the solvent the product was purified by column chromatography (silica, heptane/EtOAc 4:1 to 1:1).

Workup

  1. temperatureThe solution was then cooled to −78° C.
  2. temperatureto warm to room temperature
  3. customquenched with 50 mL 1 M sodium bicarbonate
  4. extractionextracted with DCM (2×50 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationAfter filtration and evaporation of the solvent the product
  7. customwas purified by column chromatography (silica, heptane/EtOAc 4:1 to 1:1)

Sources & evidence

ORD record
ord-0606424a02184083940e5ab8d87052e4
Source dataset
uspto-grants-2016_05
Patent number
US09346816B2

Reaction notes

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