Acetyl chloride → Methyl 1-acetyl-5-[4-(2-hydroxyethyl)phenyl]piperidine-3-carboxylate

HRID 220047Notes

Reaction equation

[OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][NH:14][CH2:13][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:11]2)=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:27](Cl)(=[O:29])[CH3:28]>ClCCl>[C:27]([N:14]1[CH2:15][CH:10]([C:7]2[CH:6]=[CH:5][C:4]([CH2:3][CH2:2][OH:1])=[CH:9][CH:8]=2)[CH2:11][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:13]1)(=[O:29])[CH3:28]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 5.58 g (9.33 mmol, purity 44%) of the compound from Example 56A in dichloromethane (80 ml) was admixed with 2.60 ml (1.89 g, 18.7 mmol) of triethylamine and then cooled to 0° C. At this temperature, 0.33 ml (0.37 g, 4.67 mmol) of acetyl chloride was added dropwise and the mixture was stirred for 2 h. A further 0.13 ml (0.15 g, 1.86 mmol) of acetyl chloride was added and the mixture was stirred for 1 h. Subsequently, the reaction solution was washed with aqueous 1 N hydrochloric acid, and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 30:1), and the crude product obtained was purified once more by means of preparative HPLC. Yield: 1.17 g (41% of theory)

Workup

stirringthe mixture was stirred for 1 h
washSubsequently, the reaction solution was washed with aqueous 1 N hydrochloric acid
dry with materialthe organic phase was dried over magnesium sulphate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 30:1)

Sources & evidence

ORD record: ord-2f948137880142c3ac1ef6a8e42bd335
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202862B2

Reaction notes

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