Methyl 4-(bromomethyl)benzoate → HCID 117665485, compound

HRID 2170738Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:11]=[C:12]([C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH2:18][CH2:19][C:20]3=[O:25])[CH:13]=[CH:14][CH:15]=1.Br[CH2:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=1>C1COCC1>[Cl:9][C:10]1[CH:11]=[C:12]([C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH2:18][CH:19]([CH2:27][C:28]2[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=2)[C:20]3=[O:25])[CH:13]=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of lithium diisopropylamide (2.0 M in THF, 0.49 mL, 0.98 mmol) was added to a solution of 4-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-one (235 mg, 0.97 mmol) in THF (3.3 mL) at −78° C. After 1 h at −78° C., a solution of methyl 4-(bromomethyl)benzoate (229 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 1 h at 0° C., the reaction was quenched with saturated aqueous NH4Cl (50 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 20 mg (5%) of methyl 4-((4-(3-chlorophenyl)-1-oxo-2,3-dihydro-1H-inden-2-yl)methyl)benzoate.

Workup

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

Sources & evidence

ORD record: ord-f8962722908542d2899104d8133245d5
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051294B2

Reaction notes

Loading…