Toluene-4-sulfonic acid 6-chloro-2-oxo-2H-1-benzopyran-4-yl ester → 4-(6-Chloro-2-oxo-2H-1-benzopyran-4-yl)-butyronitrile

HRID 495150Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9](=[O:11])[CH:8]=[C:7](OS(C3C=CC(C)=CC=3)(=O)=O)[C:6]=2[CH:23]=1.[Br-].[C:25]([CH2:27][CH2:28][CH2:29][Zn+])#[N:26]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9](=[O:11])[CH:8]=[C:7]([CH2:29][CH2:28][CH2:27][C:25]#[N:26])[C:6]=2[CH:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

Toluene-4-sulfonic acid 6-chloro-2-oxo-2H-1-benzopyran-4-yl ester (1.05 g, 3 mmol) is dissolved in THF (30 mL) under nitrogen and [P(o-tolyl)3]2PdCl2 (120 mg, 0.15 mmol) is added 3-cyanopropylzinc bromide (9 mL of a 0.5 M solution in THF, 4.5 mmol) is added and the resulting yellow solution is stirred at 60° C. for 2 hrs. Silica gel is added to the dark red reaction mixture, which is concentrated in vacuo and purified by flash column chromatography eluting with CH2Cl2 and gradually increasing polarity to 1% MeOH—CH2Cl2 to give a residue which is triturated with Et2O to give the title compound (0.54 g, 73%) as a cream solid. 1H NMR (DMSO-d6, 400 MHz) d 7.92 (1H, d, J=2 Hz), 7.68 (1H, dd, J=9, 2 Hz), 7.46 (1H, d, J=9 Hz), 6.47 (1H, s), 2.90 (2H, t, J=7 Hz), 2.63 (2H, t, J=7 Hz), 1.94 (2H, q, J=7 Hz). LCMS (MeCN—H2O, MeCN—H2O, Luna 3 m C18(2) 30×4.6mm; (ESI Pos.) calcd for C13H10ClNO2 m/z [M+H]=248; found [no mass ion detected].

Workup

additionis added
additionSilica gel is added to the dark red reaction mixture, which
concentrationis concentrated in vacuo
custompurified by flash column chromatography
washeluting with CH2Cl2
temperaturegradually increasing polarity to 1% MeOH—CH2Cl2
customto give a residue which
customis triturated with Et2O

Sources & evidence

ORD record: ord-a75ea56a91f6433281c39ce7cacd9627
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07538233B2

Reaction notes

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