Acetonitrile → Methyl 3-(6-methyl-1-(pyridin-2-ylsulfonyl)-1H-indol-2-yl)acrylate

HRID 589602Notes

Reaction equation

[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.C(#N)C.[C:23]([O:27][CH3:28])(=[O:26])[CH:24]=[CH2:25]>CCOC(C)=O.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([CH:25]=[CH:24][C:23]([O:27][CH3:28])=[O:26])[N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

In a sealed tube, 44 (9.60 g, 35.2 mmol), copper (II) acetate monohydrate (14.05 g, 70.4 mmol), and PdCl2(CH3CN)2 (0.91 g, 3.5 mmol) were placed under a nitrogen atmosphere. Acetonitrile (60 mL) was added followed by methyl acrylate (9.52 mL, 105.6 mmol). The mixture was heated at 110° C. for 20 h, allowed to reach rt, diluted with EtOAc, and washed with water and brine. The combined organic layers were dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography eluting with a linear gradient ranging from 0 to 20% EtOAc-hexanes to provide 3.86 g (30%) of product 45 as a pale yellow solid. 1H NMR (300 MHz, CDCl3) δ 2.46 (s, 3H), 3.81 (s, 3H), 6.39 (d, J=16 Hz, 1H), 6.97 (s, 1H), 7.06-7.08 (m, 1H), 7.39 (d, J=8 Hz, 1H), 7.40-7.45 (m, 1H), 7.84-7.90 (m, 1H), 7.94-7.96 (m, 1H), 8.06 (dt, J=1, 8 Hz, 1H), 8.42 (d, J=16 Hz, 1H), 8.52-8.54 (m, 1H). LC-MS (CI): m/z 357.1 [(M+H)+ C18H16N2O4S requires 356.08].

Workup

customto reach rt
washwashed with water and brine
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography
washeluting with a linear gradient

Sources & evidence

ORD record: ord-ad51fc9fbb514ade81497d40c46a5594
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233921B2

Reaction notes

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