Methyl 4-(bromomethyl)benzoate → HCID 117665522, compound

HRID 1482446Notes

Reaction equation

HRID 1482446 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]([F:29])([F:28])[C:11]1[CH:12]=[C:13]([C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH2:19][CH2:20][CH2:21][C:22]3=[O:27])[CH:14]=[CH:15][CH:16]=1.Br[CH2:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=1>C1COCC1>[O:27]=[C:22]1[C:23]2[C:18](=[C:17]([C:13]3[CH:14]=[CH:15][CH:16]=[C:11]([C:10]([F:28])([F:29])[F:9])[CH:12]=3)[CH:26]=[CH:25][CH:24]=2)[CH2:19][CH2:20][CH:21]1[CH2:31][C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 256687Methyl 4-(bromomethyl)benzoateHCID 2724682Lithium diisopropylamideHCID 117665489HCID 117665489, compound

Product 1

HCID 117665522HCID 117665522, compoundYield 8.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of lithium diisopropylamide (2.0 M in THF, 0.8 mL, 1.6 mmol) was added to a solution of 5-(3-(trifluoromethyl)phenyl)-3,4-dihydronaphthalen-1(2H)-one (435 mg, 1.5 mmol) in THF (5 mL) at −78° C. After 1 h at −78° C., a solution of methyl 4-(bromomethyl)benzoate (378 mg, 1.65 mmol) in THF (2.5 mL) was added via cannula. The reaction mixture was allowed to warm to room temperature naturally. After stirring at room temperature overnight, the reaction was quenched with saturated aqueous NH4Cl (25 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The resulting crude residue was purified by combiflash (40 g column, hexanes→40% EtOAc/hexanes, gradient) to afford 55 mg (8%) of methyl 4-((1-oxo-5-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-2-yl)methyl)benzoate.

Workup

  1. customthe reaction was quenched with saturated aqueous NH4Cl (25 mL)
  2. extractionextracted with EtOAc (3×50 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting crude residue was purified by combiflash (40 g column, hexanes→40% EtOAc/hexanes, gradient)

Sources & evidence

ORD record
ord-d9cb430f1f36444aa0c8ac045fb9bcbd
Source dataset
uspto-grants-2016_08
Patent number
US09415027B2

Reaction notes

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