Methanol → 3-(4-Bromophenyl)cyclobutane-1-carboxylic acid

HRID 575031Notes

Reaction equation

HRID 575031 reaction equation
CO.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:13][CH:12]([C:14]([O:16]C)=[O:15])[CH2:11]2)=[CH:6][CH:5]=1.[OH-].[Na+]>O>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:11][CH:12]([C:14]([OH:16])=[O:15])[CH2:13]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 53418991Methyl 3-(4-bromophenyl)cyclobutane-1-carboxylate

Product 1

HCID 233604313-(4-Bromophenyl)cyclobutane-1-carboxylic acidYield 63.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Into a 20-L 4-necked round-bottom flask was placed methanol (5 L), methyl 3-(4-bromophenyl)cyclobutane-1-carboxylate (2175 g, 8.08 mol, 1.00 equiv), followed by the addition of a solution of sodium hydroxide (1623 g, 40.58 mol, 5.02 equiv, 5 M) in water (5 L). The resulting solution was stirred at 80° C. for 3 h, cooled to 30° C. and concentrated under vacuum. The resulting solution was diluted with 10 L of H2O and 8 L of DCM, and then extracted with 2×2 L of dichloromethane. The pH value of the combined aqueous layers was adjusted to 5-6 with hydrogen chloride (6 mol/L). The resulting solution was extracted with 3×4 L of dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was triturated with 1.5 L of hexane and 300 mL of EA. The solids were collected by filtration. The filtrate was concentrated under vacuum and combined with the previous solids to afford 1312 g (crude) of 3-(4-bromophenyl)cyclobutane-1-carboxylic acid as a dark red solid.

Workup

  1. customInto a 20-L 4-necked round-bottom flask was placed
  2. temperaturecooled to 30° C.
  3. concentrationconcentrated under vacuum
  4. additionThe resulting solution was diluted with 10 L of H2O and 8 L of DCM
  5. extractionextracted with 2×2 L of dichloromethane
  6. extractionThe resulting solution was extracted with 3×4 L of dichloromethane
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe residue was triturated with 1.5 L of hexane and 300 mL of EA
  10. filtrationThe solids were collected by filtration
  11. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-0ef46f212fa9482a9c658a483af7180e
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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