Hydrochloric Acid → 2,2,4,6,7-Pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine hydrochloride

HRID 29121Notes

Reaction equation

[OH:1][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[C:5]([NH:10]C=O)=[C:4]([CH3:13])[C:3]=1[C:14]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)=[C:15]([CH3:17])[CH3:16].[ClH:25]>C(O)C(C)C>[ClH:25].[CH3:16][C:15]1([CH3:17])[CH:14]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[C:3]2[C:4]([CH3:13])=[C:5]([NH2:10])[C:6]([CH3:9])=[C:7]([CH3:8])[C:2]=2[O:1]1

Participants

Conditions

Temperature: 2.5 °C

Procedure

To a mixture of N-[4-hydroxy-3-[2-methyl-1-(4-methylphenyl)-1-propenyl]-2,5,6-trimethylphenyl]formamide (740 g) and isobutanol (2220 ml) was added concentrated hydrochloric acid (2220 ml) under nitrogen stream and the mixture was refluxed under heating for 5 hr. The mixture was stirred at 0 to 5° C. for 1 hr. The crystals were collected by filtration and washed with toluene to give 2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine hydrochloride. This hydrochloride was dissolved in a mixed solution of methanol (5180 ml)/water (740 ml) at 55 to 60° C. To the solution was added dropwise 25% aqueous ammonium at 50° C. to adjust the pH to 8.5, and the mixture was stirred for 30 min. The precipitated crystals were collected by filtration and washed with methanol/water (1:1) to give the title compound (587.2 g, yield 87.4%).

Workup

temperaturethe mixture was refluxed
temperatureunder heating for 5 hr
filtrationThe crystals were collected by filtration
washwashed with toluene

Sources & evidence

ORD record: ord-3cb17ac7a19c4dad910bcd36a8229307
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07420070B2

Reaction notes

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