Formaldehyde → Benzoic acid, 3-methoxy-, chloromethyl ester

HRID 1496793Notes

Reaction equation

[C:1]([OH:11])(=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=1.S(Cl)(Cl)=O.[C:16]([Cl:26])(=O)C1C=CC=C(OC)C=1.C=O>[Cl-].[Zn+2].[Cl-]>[CH3:9][O:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:1]([O:11][CH2:16][Cl:26])=[O:10]

Participants

Conditions

Temperature: 80 °C

Procedure

A similar procedure (Lu, M. C. et al. J. Med. Chem. 1987, 30, 273-278 and Iyer, R. P. et al. Synth. Commun. 1995, 25, 2739-2749) to that described for the preparation of 50 was followed using m-anisic acid (4.1 g, 26.9 mmol) and thionyl chloride (4 mL), under reflux for 1 h. A mixture of crude m-anisoyl chloride, paraformaldehyde (808 mg, 26.9 mmol) and zinc chloride (28 mg, 0.21 mmol) was then stirred at 80° C. for 16 h. Purification by flash chromatography (hexane/ethyl acetate 19:1) afforded chloromethyl m-methoxybenzoate (47) as a pale green oil (1.4 g, 6.86 mmol, 26%). 1H NMR 3.86 (3H, s, OMe), 5.95 (2H, s, CH2), 7.14-7.17 (1H, m, Ar), 7.36-7.40 (1H, m, Ar), 7.58-7.59 (1H, m, Ar), 7.66-7.69 (1H, m, Ar).

Workup

temperatureunder reflux for 1 h
customPurification by flash chromatography (hexane/ethyl acetate 19:1)

Sources & evidence

ORD record: ord-89260c74591d47e0aae496e348ab07b9
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09198420B2

Reaction notes

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