Toluene → HCID 68211704, compound

HRID 406125Notes

Reaction equation

Cl.Cl.[CH3:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1.CC([O-])(C)C.[Na+].[C:20]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1)([CH3:23])([CH3:22])[CH3:21].C1(C)C=CC=CC=1>CO.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:20]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([N:11]2[CH2:12][CH2:13][C@H:9]([N:5]3[CH2:6][CH2:7][CH2:8][C@@H:4]3[CH3:3])[CH2:10]2)=[CH:28][CH:27]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

Conditions

Temperature: 80 °C

Procedure

(2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl dihydrochloride (1.1 g, 4 mmol) was treated with NaOt-Bu (1.1 g, 2equiv) in MeOH (30 mL), filtered, and concentrated. To this flask was charged with tert-Butyl-4-bromo-benzoate (1 g, 3.89 mmol), sodium tert-butoxide 538 mg, 5.6 mmol), tris(dibenzylideneacetone)dipalladium-(0) (35 mg, 0.039 mmol), BINAP (72 mg, 0.116 mmol), and toluene (40 mL) under argon. The reaction flask was heated to 80° C. (external) for 24 h with stirring until the starting material had been completely consumed as judged by TLC analysis. The mixture was allowed to cool to room temperature, taken up in DCM (50 mL), filtered, and concentrated. The crude product was then purified further by flash chromatography on a silica gel column eluted with 0-5% of 7N NH3/MeOH in DCM to get 1.02 g (80%) of the title compound as a yellow oil.

Workup

filtrationfiltered
concentrationconcentrated
customhad been completely consumed
temperatureto cool to room temperature
filtrationfiltered
concentrationconcentrated
customThe crude product was then purified further by flash chromatography on a silica gel column
washeluted with 0-5% of 7N NH3/MeOH in DCM

Sources & evidence

ORD record: ord-d079592f1de045d9a94c5eb82aeff62a
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754095B2

Reaction notes

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