Methyl 4-(bromomethyl)benzoate → HCID 117665501, compound

HRID 2170739Notes

Reaction equation

HRID 2170739 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]1([C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[CH2:21][CH2:22][C:23]3=[O:28])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1.Br[CH2:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=1>C1COCC1>[C:9]1([C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[CH2:21][CH:22]([CH2:30][C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[C:23]3=[O:28])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 256687Methyl 4-(bromomethyl)benzoateHCID 2724682Lithium diisopropylamideHCID 105541411HCID 105541411, compound

Product 1

HCID 117665501HCID 117665501, compoundYield 13.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of lithium diisopropylamide (2.0 M in THF, 0.50 mL, 1.0 mmol) was added to a solution of 4-(naphthalen-1-yl)-2,3-dihydro-1H-inden-1-one (254 mg, 0.98 mmol) in THF (3.4 mL) at −78° C. After 1 h at −78° C., a solution of methyl 4-(bromomethyl)benzoate (230 mg, 1.0 mmol) in THF (1.7 mL) was added via cannula. After 1 h at −78° C., the mixture was allowed to slowly warm to 0° C. After 30 min at 0° C., the reaction was quenched with saturated aqueous NH4Cl (25 mL), diluted with water (10 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→30% EtOAc/hexanes, gradient) to afford 53 mg (13%) of methyl 4-((4-(naphthalen-1-yl)-1-oxo-2,3-dihydro-1H-inden-2-yl)methyl)benzoate.

Workup

  1. waitAfter 1 h at −78° C.
  2. waitAfter 30 min at 0° C.
  3. customthe reaction was quenched with saturated aqueous NH4Cl (25 mL)
  4. additiondiluted with water (10 mL)
  5. extractionextracted with EtOAc (3×50 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting crude residue was purified by combiflash (40 g column, hexanes→30% EtOAc/hexanes, gradient)

Sources & evidence

ORD record
ord-ee00e14dea954f8987e3319db629ab39
Source dataset
uspto-grants-2015_06
Patent number
US09051294B2

Reaction notes

Loading…