(2-Chloro-7-cyano-naphthalen-1-yl)-acetic acid ethyl ester → (2-Chloro-7-formyl-naphthalen-1-yl)-acetic acid ethyl ester

HRID 1968710Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:19])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]#N)[CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:18])[CH3:2].[PH2]([O-])=[O:21].[Na+]>O.N1C=CC=CC=1.C(O)(=O)C.[Ni]>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:16]=[O:21])[CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:18])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

(2-Chloro-7-cyano-naphthalen-1-yl)-acetic acid ethyl ester (5.53 g, 20.20 mmol) is dissolved in a mixture of water (70 ml), pyridine (130 ml) and glacial acetic acid (70 ml). Sodium hypophosphite (17.13 g, 161.62 mmol) and Raney nickel (13 g) are added at RT. The reaction mixture is heated to 100° C. for 1 h. TLC analysis indicates complete consumption of starting material. The reaction mixture is cooled to RT, filtered through Celite and concentrated on a rotary evaporator. The residue is taken up in 2 M aqueous HCl. Extraction with EtOAc, removal of solvent and purification by FCC (hexane/EtOAc 5:1) yields the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.28 (t, J=8.8 Hz, 3H), 4.22 (q, J=8.8 Hz, 2H), 4.39 (s, 2H), 7.68 (d, J=9.9 Hz, 1H), 7.83 (d, J=9.9 Hz, 1H), 7.95-8.03 (m, 2H), 8.48 (s, 1H), 10.2 (s, 1H). ES−-MS: 275.3, 277.3 [M+H]+.

Workup

customconsumption of starting material
temperatureThe reaction mixture is cooled to RT
filtrationfiltered through Celite
concentrationconcentrated on a rotary evaporator
extractionExtraction
customwith EtOAc, removal of solvent and purification by FCC (hexane/EtOAc 5:1)

Sources & evidence

ORD record: ord-be894b97418147d3b37c99714c047e5d
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426440B2

Reaction notes

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