Pyrrolidine → 6-methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)chroman-4-one

HRID 714604Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10](=[O:12])[CH3:11].[CH3:13][C@@H:14]1[CH2:18][CH2:17][N:16]([C@@H:19]([CH3:30])[CH2:20][O:21][C:22]2[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=2)[CH2:15]1.N1CCCC1>CO>[CH3:9][O:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[O:1][CH:26]([C:25]1[CH:28]=[CH:29][C:22]([O:21][CH2:20][C@@H:19]([N:16]3[CH2:17][CH2:18][C@@H:14]([CH3:13])[CH2:15]3)[CH3:30])=[CH:23][CH:24]=1)[CH2:11][C:10]2=[O:12]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 1-(2-hydroxy-5-methoxyphenyl)ethanone (1 g, 6 mmol), 4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)benzaldehyde (1.5 g, 6.08 mmol), and pyrrolidine (0.12 mL, 1.5 mmol) in methanol (12 mL) was heated at 50° C. for two days. After cooling, the solvent was removed and the residue was purified by silica gel chromatography to afford 427 mg of 6-methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)chroman-4-one as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 7.45 (d, 2H), 7.22-7.18 (m, 2H), 7.03 (d, 1H), 6.98 (d, 2H), 5.52 (dd, 1H), 4.04 (m, 1H), 3.83 (m, 1H), 3.80 (s, 3H), 3.24 (dd, 1H), 2.87 (m, 1H), 2.76 (dd, 1H), 2.67 (m, 2H), 2.58 (m, 1H), 2.11 (m, 2H), 1.91 (m, 1H), 1.22 (m, 1H), 1.13 (d, 3H), 0.97 (d, 3H).

Workup

temperatureAfter cooling
customthe solvent was removed
customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-567d230425a74a6c85629d030ca6b6d4
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187460B2

Reaction notes

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