Sodium Bicarbonate → N-[2-(S)-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methyl-3cyano-2methoxy-1-naphthamide

HRID 1355378Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:13][CH2:14][OH:15])[CH2:10][NH:11][CH3:12])[CH:5]=[CH:6][C:7]=1[Cl:8].C(=O)(O)[O-].[Na+].[C:21]([C:23]1[C:24]([O:36][CH3:37])=[C:25]([C:33](Cl)=[O:34])[C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[CH:28][CH:27]=2)#[N:22]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:13][CH2:14][OH:15])[CH2:10][N:11]([CH3:12])[C:33]([C:25]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:32]=[C:23]([C:21]#[N:22])[C:24]=2[O:36][CH3:37])=[O:34])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of N-[(S)-2-(3,4-Dichlorophenyl)-4-hydroxybutyl]-N-methylamine (Miller, S.C., WO 9512577) in DCM was combined with 10% aqueous sodium bicarbonate solution. The mixture was cooled to 0° C. and a solution of 3-cyano-2-methoxy-1-naphthoyl chloride in DCM was added dropwise over 30 min. After stirring overnight at room temperature, the organic phase was concentrated and purified by column chromatography to afford N-[2-(S)-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methyl-3-cyano-2-methoxy-1-naphthamide. 1H NMR (300 MHz, DMSO-d6) δ9.70-9.64 (m), 8.67-8.57 (m), 8.07-7.97 (m), 7.80 (s), 7.72-7.55 (m), 7.52-7.48 (m), 7.40-7.33 (m), 7.12-7.10 (d), 7.04-7.02 (d), 6.87-6.83 (d), 6.37-6.29 (d) 4.53-4.44 (t), 4.11-4.00 (m), 3.94 (s), 3.92 (s), 3.91-3.73 (m), 3.71 (s), 3.45-3.38 (m), 3.33 (s) (s), 3.14 (s), 2.97-2.95 (d), 2.63 (s), 2.60 (s); MS APCI, m/z=455 (M+). This compound was characterized as a mixture of atropoisomers.

Workup

concentrationthe organic phase was concentrated
custompurified by column chromatography

Sources & evidence

ORD record: ord-2a7396e185b945cea3fcea6ddbd1a579
Source dataset: uspto-grants-2003_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06586432B2

Reaction notes

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