Dichloromethane → 4-Methoxyphenylacetyl chloride

Participants

Reaction Conditions

Reaction Steps

8-Ethano-1-(p-hydroxybenzyl)-2-methyl- 1,2,3,4,5,6,7,8-octahydroisoquinoline (10). A 100 mL three-necked flask was dried for 24 h at 210° C. While cooling under a stream of dry nitrogen, the flask was immersed in an ethanol/dry ice bath and cooled to -75° C. Boron tribromide (300 μl, 3.16 mmole) was introduced, followed by 10 ml of dry dichloromethane. Purified 9 (224 mg, 0.754 mmole), as the base, in 30 ml of dry dichloromethane was added in a dropwise fashion. Thirty minutes after the addition of 9, the stirring was stopped, the nitrogen was replaced by a calcium sulfate drying tube, and the mixture was left in the cold for 12 h. After refluxing for 1 h, the reaction mixture was recooled in an ice bath and 3.5 ml of 10% ammonium hydroxide was slowly added and a flocculent precipitate formed. After stirring for 15 min, the cold bath was removed and 50 ml of water was added. The subsequent isolation of the product was conducted in the dark to minimize photooxidation. The phases were separated, the dichloromethane was removed in vacuo and the residue was dissolved in ethyl ether. The aqueous phase (pH 8.4) was adjusted to pH 9.1 with 10% ammonium hydroxide and extracted eight times with 20 ml portions of ether. All ether phases were combined, dried (Na2SO4), and concentrated to give a yellow oil. An attempt was made to purify this base by methansulfonate salt formation, but this salt form resisted crystallization. The hydrochloride salt was made and recrystallized from acetone/ethanol/ethyl ether in 29% yield. There was evidence of additional product in the mother liquor but it resisted crystallization: mp (sealed tube) 218°-220° C. sublime; 1H NMR (base in CDCl3) δ 6.67 (AA'BB', 4 H aromatic), 4.58 (s, 1 H, OH), 2.87-3.30 (m, 1 H, 1-H), 2.43-2.87 (m, 4 H, 1-CH2, 3-H2), 2.33 (s, 3 H, NCH3), 1.90-2.27 (m, 4 H, 4-H2, 5-H, 8-H), 0.93-1.72 (m, 8 H, remaining protons); IR (base, neat) 3300 (OH stretch) cm -1 ; mass spectrum, m/z 283 (M+), 176 (M+ -p-hydroxybenzyl, base), 148 (retro-Diels-Alder), 107 (p-hydroxybenzyl+), 106 (p-hydroxybenzyl-1+), 42 (CH2 =N=CH2+).

Provenance & Evidence