Hydrochloric Acid → 4-(Chloromethyl)-2-(cyclopentyloxy)-1-methoxybenzene

HRID 1250311Notes

Reaction equation

[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:10]O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:17].C(=O)(O)[O-].[Na+].COC(C)(C)C>C1(C)C=CC=CC=1>[Cl:17][CH2:10][C:9]1[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:7]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:8]=1

Participants

Conditions

Temperature: 22.5 °C

Procedure

A 12 liter round bottom flask equipped with an overhead stirrer, internal thermometer, and a reflux condensor equipped with a nitrogen inlet was flushed with nitrogen. The flask was charged with 3-cyclopentyloxy-4-methoxybenzyl alcohol (495 g, 2.2 mol, 1 equivalent) in a solution of toluene. To the vigorously stirred reaction at 22° C. was added concentrated hydrochloric acid (600 g, 2.75 equivalents). The reaction was maintained at 20 to 25° C. for 30 minutes. The top organic layer was isolated and the bottom acidic layer was discarded. To the top organic layer was charged a solution of 10% sodium bicarbonate (550 g, 0.65 mol, 0.36 equivalents) and t-butyl methyl ether (814 g). The contents of the flask were vigorously stirred, and allowed to settle. The product, 4-chloromethyl-2-cyclopentyloxy-1-methoxybenzene, was isolated as a solution in toluene and t-butyl methyl ether (96.8% solution yield). This was used directly in the next step.

Workup

customA 12 liter round bottom flask equipped with an overhead stirrer
custominternal thermometer, and a reflux condensor equipped with a nitrogen inlet
customwas flushed with nitrogen
customTo the vigorously stirred reaction at 22° C.
customThe top organic layer was isolated

Sources & evidence

ORD record: ord-54c88aa168f44e1fa028f2dda8bd940c
Source dataset: uspto-grants-2002_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06337408B1

Reaction notes

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