Hydrochloric Acid → 4-(3,5-Di-tert-butylphenyl)-2-cyclopropyl indene

HRID 923730Notes

Reaction equation

Br[C:2]1[CH2:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]1[CH:16]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:14]=[C:13]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:12]=1)[CH:7]=[CH:6][CH:5]=2.[CH:25]1([Mg]Br)[CH2:27][CH2:26]1.O1CCCC1.Cl>C1(C)C=CC=CC=1>[CH:25]1([C:2]2[CH2:3][C:4]3[C:9]([CH:10]=2)=[C:8]([C:11]2[CH:12]=[C:13]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:14]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:16]=2)[CH:7]=[CH:6][CH:5]=3)[CH2:27][CH2:26]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of compound 6 (16.1 g, 42.0 mmol, 1 equiv) and anhydrous toluene (200 mL) was treated with [1,1′-bis(diphenylphos-phino)ferrocene]dichlopalladium(II) DCM adduct (3.43 g, 4.2 mmol, 0.1 equiv). After stirring for 10 minutes, 0.5 M cyclopropylmagnesium bromide in tetrahydrofuran (420 mL, 210 mmol, 5 equiv) was added dropwise. The reaction was heated at 60° C. overnight. The reaction was cooled with an ice bath, acidified with 1N HCl to pH 3 and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with saturated brine (800 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified on an AnaLogix (65-200 g) column with dry-loading, eluting with heptanes to give compound 7 (7.0 g, 48% yield) as a white solid.

Workup

temperatureThe reaction was cooled with an ice bath
extractionextracted with ethyl acetate (3×500 mL)
washThe combined organic layers were washed with saturated brine (800 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified on an AnaLogix (65-200 g) column
customwith dry-loading
washeluting with heptanes

Sources & evidence

ORD record: ord-ee36ac519c67450ebb7a1db6ea0c4e34
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09279024B2

Reaction notes

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