Carbon Dioxide → HCID 51064101, compound

HRID 566619Notes

Reaction equation

HRID 566619 reaction equation
[OH:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][C@H:7]([CH3:11])[C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[K].C(=O)([O-])[O-].[K+].[K+].C(=O)=O.[Cl:24][C:25]1[CH:26]=[C:27]([F:32])[C:28](F)=[N:29][CH:30]=1.[CH2:33](Cl)[C:34]#[CH:35]>CN(C=O)C.C1(C)C=CC=CC=1>[C:33]([O:9][C:8](=[O:10])[C@H:7]([O:6][C:5]1[CH:4]=[CH:3][C:2]([O:1][C:28]2[C:27]([F:32])=[CH:26][C:25]([Cl:24])=[CH:30][N:29]=2)=[CH:13][CH:12]=1)[CH3:11])#[C:34][CH3:35]

Participants

9

Reactant 6

HCID 280Carbon DioxideHCID 11430Potassium Carbonate2×HCID 122213-Chloro-1-propyneHCID 179741(R)-2-(4-Hydroxyphenoxy)propionic acidHCID 27832485-Chloro-2,3-difluoropyridineHCID 5462222Potassium

Product 1

HCID 51064101HCID 51064101, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

182 g of (R)-2-(p-hydroxyphenoxy)-propionic acid 100% (1 mol) in 600 g of DMF are converted into the corresponding potassium salt by adding 69 g of potassium carbonate powder (0.5 mols) at 70° C. whilst cleaving the CO2. To this solution are added 193 g of potassium carbonate powder (1.4 mols) and then, at a temperature of 70-75° C., 165 g of 5-chloro-2,3-difluoropyridine (1.1 mols) are added over the course of 30 minutes. After 4 hours, the compound of formula V thus obtained is reacted totally, by measuring in 86 g of propargyl chloride (1.15 mols) as a 60-70% toluene solution over the course of 2 hours directly, without isolation, at a temperature of 70-75° C., to form the (R)(+)-2-[4-(5-chloro-3-fluoropyridin-2-yloxy)-phenoxy]-propionic acid propinyl ester. The salts are filtered off, washed with 300 g of DMF in portions, and the filtrate is concentrated to the melt on a rotary evaporator under vacuum at a temperature of 120°C. The crude melt of the (R)(+)-2-[4-(5-chloro-3-fluoropyridin-2-yloxy)-phenoxy]-propionic acid propinyl ester is mixed at a temperature of 50°C. with 300 g of ethanol/water 9:1, seeded at a temperature of 30 to 35° C. and cooled to a temperature of 0 to 50° C. The crystal pulp is added to a suction filter, washed with 70 g of ethanol/water 9:1, and dried under vacuum at a temperature of 30 °C. 307 g of active substance are obtained with a content of 97 % (GC), corresponding to a yield of 85% of theory, based on (R)-2-(p-hydroxyphenoxy)-propionic acid.

Workup

  1. customthe compound of formula V thus obtained
  2. customis reacted totally

Sources & evidence

ORD record
ord-bc73938e01534a3b9a50e6ac18fcc24c
Source dataset
uspto-grants-2001_01
Patent number
US06175018B1

Reaction notes

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