Benzyl Bromide → (1R,2r)-benzyl2-methylcyclopropanecarboxylate

HRID 2422695Notes

Reaction equation

HRID 2422695 reaction equation
[CH3:1][CH:2]1[CH2:4][CH:3]1[C:5]([OH:7])=[O:6].[OH-].[Na+].[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CCCCCCCCCC[N+](CCCCCCCCCC)(CCCCCCCCCC)C.CCCCCCCCC[N+](CCCCCCCCC)(CCCCCCCCC)C.CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].[Cl-].[Cl-]>[CH3:1][C@@H:2]1[CH2:4][C@H:3]1[C:5]([O:7][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:6]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 14798Sodium HydroxideHCID 998732-Methylcyclopropanecarboxylic acid

Product 1

HCID 67180743(1R,2r)-benzyl2-methylcyclopropanecarboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 16218603Methyl-tri(nonyl)azanium;methyl(trioctyl)azanium;tris-decyl(methyl)azanium;trichlorideCatalyst

Conditions

Temperature
45 °C

Procedure

A mixture of 2-methylcyclopropanecarboxylic acid (commercial product which is a cis-trans mixture, 75.0 g, 0.75 mol) and 1 N NaOH (900 mL, 0.90 mol) is warmed and stirred at 45° C. To the stirring solution is added benzyl bromide (131.0 mL, 1.10 mol) and methyltrialkyl(C8-C10)ammonium chloride (Adogen™ 464, 37.5 g). The mixture is stirred at 40-45° C. for 4 h, cooled to room temperature, and extracted with ethyl ether (800 mL). The organic layer is dried (MgSO4) and evaporated to a liquid. Chromatography over silica gel, eluting with hexanes gradually increasing to 5% ethyl acetate in hexanes, provides the racemic benzyl trans-2-methylcyclopropanecarboxylate as a liquid (132.2 g, 93%); 1H NMR (DMSO-d6) δ 7.40 (m, 5H), 5.05 (s, 2H), 1.43 (m, 1H), 1.30 (m, 1H), 1.06 (d, J=6.0 Hz, 3H), 1.02 (m, 2H), 0.74 (m, 1H). [Note: If NMR reveals the presence of a minor amount of cis isomer, it is removable by the chiral HPLC separation which may be carried out as described above.]

Workup

  1. temperatureis warmed
  2. stirringThe mixture is stirred at 40-45° C. for 4 h
  3. temperaturecooled to room temperature
  4. extractionextracted with ethyl ether (800 mL)
  5. dry with materialThe organic layer is dried (MgSO4)
  6. customevaporated to a liquid
  7. washChromatography over silica gel, eluting with hexanes
  8. temperaturegradually increasing to 5% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-fe625043e10b472896745214d47a8ee0
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Reaction notes

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