Phosgene → (E)-5-(2,2-Difluoro-hex-5-ynoyloxymethylene)-2,4-dioxo-thiazolidine-3-carboxylic acid 5-chloro-thiophen-2-ylmethyl Ester

HRID 583791Notes

Reaction equation

HRID 583791 reaction equation
[F:1][C:2]([F:18])([CH2:14][CH2:15][C:16]#[CH:17])[C:3]([O:5]/[CH:6]=[C:7]1\[C:8](=[O:13])[NH:9][C:10](=[O:12])[S:11]\1)=[O:4].C(Cl)(Cl)=O.ClC(Cl)(O[C:27](=[O:33])[O:28][C:29](Cl)(Cl)Cl)Cl.[Cl:35][C:36]1[S:40][C:39](CO)=[CH:38][CH:37]=1>C1COCC1>[Cl:35][C:36]1[S:40][C:39]([CH2:29][O:28][C:27]([N:9]2[C:8](=[O:13])/[C:7](=[CH:6]\[O:5][C:3](=[O:4])[C:2]([F:1])([F:18])[CH2:14][CH2:15][C:16]#[CH:17])/[S:11][C:10]2=[O:12])=[O:33])=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 94429TriphosgeneHCID 12554178(5-Chlorothiophen-2-yl)methanolHCID 86587878(E)-5-(2,2-difluoro-hex-5-ynoyloxymethylidenyl)-2,4-thiazolidindione

Product 1

HCID 20818691(E)-5-(2,2-Difluoro-hex-5-ynoyloxymethylene)-2,4-dioxo-thiazolidine-3-carboxylic acid 5-chloro-thiophen-2-ylmethyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (E)-5-(2,2-difluoro-hex-5-ynoyloxymethylidenyl)-2,4-thiazolidindione, which may be prepared as described in Step (d) above, in THF is added 2 mol equivalents of a non-nucleophilic base such as one of those described above in Example 17, followed by 1 mol equivalent of phosgene or 0.33 mol equivalents of triphosgene, and the mixture is stirred. After stirring for from 1 minute to about 1 hour, 5-chlorothiophen-2-ylmethyl alcohol is added, and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of the desired product is formed, the reaction is partitioned between ethyl acetate and water. The organic layer is washed with 0.01 M sodium bicarbonate, water, brine, and dried over sodium sulfate. The mixture is rotary evaporated to give (E)-5-(2,2-difluoro-hex-5-ynoyloxymethylene)-2,4-dioxo-thiazolidine-3-carboxylic acid 5-chloro-thiophen-2-ylmethyl ester, which may be purified, if needed or desired, by chromatography on silica gel or crystallization.

Workup

  1. additionis added 2 mol equivalents of a non-nucleophilic base such as one of
  2. additionis added
  3. stirringthe mixture is stirred
  4. customReaction progress

Sources & evidence

ORD record
ord-8161c6bcf7e744e2914c60f8bd86d88f
Source dataset
uspto-grants-2005_08
Patent number
US06924276B2

Reaction notes

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