Formaldehyde → Chloromethyl naphthalene-2-carboxylate

HRID 1496797Notes

Reaction equation

HRID 1496797 reaction equation
C1(C(C2C=CC=CC=2)C(O[CH2:11][Cl:12])=O)C=CC=CC=1.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29]([OH:31])=[O:30].C(Cl)(=O)C(Cl)=O.C1C2C(=CC=CC=2)C=CC=1C(Cl)=O.C=O>[Cl-].[Zn+2].[Cl-]>[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29]([O:31][CH2:11][Cl:12])=[O:30]

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 71232-Naphthoic acidHCID 65578Oxalyl chlorideHCID 752462-Naphthoyl chlorideHCID 68421810HCID 68421810, compound

Product 1

HCID 71361496Chloromethyl naphthalene-2-carboxylateYield 6%

Reagents, catalysts & solvents 1

HCID 3007855ZincchlorideCatalyst

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 2-naphthoic acid (1.0 g, 5.8 mmol) and oxalyl chloride (2 mL), under reflux for 2 h. A mixture of crude 2-naphthoyl chloride, paraformaldehyde (174 mg, 5.8 mmol) and zinc chloride (6 mg, 0.04 mmol) was then stirred at 80° C. for 2 h. Purification by flash chromatography (hexane/ethyl acetate 4:1) afforded chloromethyl 2-naphthoate (53) as a colourless oil (80 mg, 0.36 mmol, 6%); 1H NMR (400 MHz, CDCl3) δ 5.98 (2H, s, CH2), 7.53-7.64 (2H, m, Ar), 7.87-7.96 (3H, m, Ar), 8.05-8.10 (1H, m, Ar), 8.65 (1H, s, Ar).

Workup

  1. temperatureunder reflux for 2 h
  2. customPurification by flash chromatography (hexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-c72ebf4983324069a701ba83f888de38
Source dataset
uspto-grants-2015_12
Patent number
US09198420B2

Reaction notes

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