Diisopropylamine → tert-Butyl 1-(3-bromo-4-chlorobenzyl)cyclopropanecarboxylate

HRID 626416Notes

Reaction equation

HRID 626416 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]1.[Br:23][C:24]1[CH:29]=[C:28]([CH2:30]Br)[CH:27]=[CH:26][C:25]=1[Cl:32].[Cl-].[NH4+]>C1COCC1>[Br:23][C:24]1[CH:29]=[C:28]([CH:27]=[CH:26][C:25]=1[Cl:32])[CH2:30][C:13]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 13676038tert-Butyl cyclopropanecarboxylateHCID 509986962-Bromo-4-(bromomethyl)-1-chlorobenzeneHCID 178418339Butyllithium

Product 1

HCID 67958496tert-Butyl 1-(3-bromo-4-chlorobenzyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

Under argon, 140.2 ml (1.0 mol) of diisopropylamine were dissolved in 1200 ml of dry THF and cooled to −30° C. 400 ml (1.0 mol) of n-butyllithium solution (2.5 M in hexane) were added dropwise. The resulting mixture was warmed to 0° C. and then cooled to −70° C. A solution of 94.8 g (0.667 mol) of tert-butyl cyclopropanecarboxylate in 750 ml THF was added to the reaction solution, with the temperature being kept below −60° C. After 4 h of stirring at −60° C., a solution of 208.6 g (0.733 mol) of 2-bromo-4-(bromomethyl)-1-chlorobenzene in 550 ml of THF was added, the temperature again being kept below −60° C. The reaction mixture was slowly warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added carefully. After phase separation, the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 4:1). This gave 95.5 g (41.4% of theory) of the title compound.

Workup

  1. temperatureThe resulting mixture was warmed to 0° C.
  2. temperaturecooled to −70° C
  3. custombeing kept below −60° C
  4. customagain being kept below −60° C
  5. temperatureThe reaction mixture was slowly warmed to RT overnight
  6. customAfter phase separation
  7. extractionthe aqueous phase was extracted with ethyl acetate
  8. dry with materialThe combined organic phases were dried over magnesium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 4:1)

Sources & evidence

ORD record
ord-1a997dccfd3240939b38c855deab7159
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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