Phosphorus oxychloride → HCID 131726604, compound

HRID 1873928Notes

Reaction equation

HRID 1873928 reaction equation
[C:1]([C:4]1[C:5]([OH:25])=[C:6]([C@@H:14]2[CH2:18][CH2:17][N:16]([CH3:19])[C@H:15]2[CH2:20][O:21][C:22](=[O:24])[CH3:23])[C:7]([O:12][CH3:13])=[CH:8][C:9]=1[O:10][CH3:11])(=[O:3])[CH3:2].[Cl:26][C:27]1[C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=[CH:29][N:28]=1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:22]([O:21][CH2:20][C@H:15]1[C@H:14]([C:6]2[C:7]([O:12][CH3:13])=[CH:8][C:9]([O:10][CH3:11])=[C:4]([C:1](=[O:3])[CH3:2])[C:5]=2[O:25][C:33](=[O:34])[C:32]2[CH:31]=[CH:30][CH:29]=[N:28][C:27]=2[Cl:26])[CH2:18][CH2:17][N:16]1[CH3:19])(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 762582-Chloronicotinic acidHCID 59318487HCID 59318487, compound

Product 1

HCID 131726604HCID 131726604, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(+/−)-trans-Acetic acid 3-(3-acetyl-2-hydroxy-4,6-dimethoxy-phenyl)-1-methyl-pyrrolidin-2-ylmethyl ester (1.65 g, 4.7 mmol) was reacted with 2-chloro-pyridine-3-carboxylic acid (2.44 g, 15.49 mmol) in the presence of dry pyridine (25 mL) and POCl3 (2.1 mL, 23.43 mmol) using the conditions described in example 52 to get trans-2-Chloro-nicotinic acid 2-(2-acetoxymethyl-1-methyl-pyrrolidin-3-yl)6-acetyl-3,5-dimethoxy-phenyl ester. This was converted in situ to the title compound (66) using NaH (1.29 g, 26.86 mmol) in 1,4-dioxane (25 mL) as described in example 26.

Sources & evidence

ORD record
ord-002fda58ea2442c88482028688f93b11
Source dataset
uspto-grants-2012_11
Patent number
US08304449B2

Reaction notes

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