Acetyl chloride → 1-[(S)-3-(2-Bromoethyl)-2,3-dihydro-1H-indol-1-yl]-ethanone

HRID 1984004Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@H:3]([CH2:10][CH2:11]O)[CH2:2]1.C(N(CC)CC)C.[C:20](Cl)(=[O:22])[CH3:21].CS(Cl)(=O)=O.[Br-:29].[Li+]>O1CCCC1>[Br:29][CH2:11][CH2:10][C@H:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([C:20](=[O:22])[CH3:21])[CH2:2]1

Participants

Conditions

Temperature: -21.5 °C

Procedure

To a cooled (−28° C.) solution of (S)-2-(2,3-dihydro-1H-indol-3-yl)ethanol (8.5 g, 0.052 mol) in tetrahydrofuran (500 mL) and triethylamine (5.6 g, 0.055 mol) was added a solution of acetyl chloride (4.0 g, 0.051 mol) in tetrahydrofuran (200 mL) over a period of 35 min at −35 to −30° C. The mixture was stirred at −25 to −18° C. for 20 min, and an additional amount of triethylamine (6.3 g, 0.062 mol) was added followed by a solution of methanesulfonyl chloride (6 g, 0.052 mol) in tetrahydrofuran (200 mL) over a period of 25 min at −12 to −3° C. The resulting mixture was filtered and concentrated in vacuo. The residue was dissolved in acetone (600 mL) and lithium bromide (21.7 g, 0.25 mol) was added. The mixture was boiled under reflux for 1 h, filtered and concentrated in vacuo. The residue was purified by flash chromatography (heptane/ethyl acetate 1:1) to give the title compound (10.6 g, 76%).

Workup

filtrationThe resulting mixture was filtered
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in acetone (600 mL)
temperatureunder reflux for 1 h
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography (heptane/ethyl acetate 1:1)

Sources & evidence

ORD record: ord-9acfbc688b504f2fb0d30d0a94315f1a
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07544685B2

Reaction notes

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