Dichloromethane → 7-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxopentoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one

HRID 615709Notes

Reaction equation

HRID 615709 reaction equation
[CH3:1][CH:2]([CH:6]([CH3:9])[CH2:7][CH3:8])[C:3]([OH:5])=[O:4].C(Cl)Cl.C(Cl)(=O)C(Cl)=O.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[S:28][C:27]3=[CH:29][N:30]([CH2:41]O)[C:31](=[O:40])[C:32]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=4)=[C:26]3[NH:25][C:24]=2[CH:43]=1>N1C=CC=CC=1>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]2[S:28][C:27]3=[CH:29][N:30]([CH2:41][O:4][C:3](=[O:5])[CH:2]([CH3:1])[CH:6]([CH3:9])[CH2:7][CH3:8])[C:31](=[O:40])[C:32]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=4)=[C:26]3[NH:25][C:24]=2[CH:43]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 131832772,3-Dimethylpentanoic acidHCID 204269037-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one

Product 1

HCID 204269047-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxopentoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-oneYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 2.06 g. of 2,3-dimethylvaleric acid (15.8 mmol). in 30 ml. of methylene chloride was cooled in a cold water bath and treated with 2.0 g. of oxalyl chloride (15.8 mmol.). The resulting solution was stirred at room temperature for 2 hours, then the methylene chloride was removed under reduced pressure. The resulting residue was added dropwise to a cold, stirred suspension of 1.2 g. of 7-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one (3.1 mmol.) in 25 ml. of pyridine. After stirring for 35 minutes, the mixture was poured onto ice-water and allowed to stand for 16 hours at room temperature, resulting in the formation of a yellow precipitate, which was collected, washed with water, air-dried, then purified using flash chromatography on silica gel, employing a mixture of 5% ethyl acetate: 95% methylene chloride as the eluent. Fractions containing the product were combined and triturated with ether to yield 7-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxopentoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a pale yellow crystalline solid (1.18 g; 76% yield) having the structural formula, ##STR22## a melting point in the range of 165°-173° C. and the following elemental analysis:

Workup

  1. additionA mixture of 2.06 g
  2. additiontreated with 2.0 g
  3. customthe methylene chloride was removed under reduced pressure
  4. additionThe resulting residue was added dropwise to a cold
  5. stirringstirred
  6. additionsuspension of 1.2 g
  7. stirringAfter stirring for 35 minutes
  8. additionthe mixture was poured onto ice-water
  9. waitto stand for 16 hours at room temperature
  10. customresulting in the formation of a yellow precipitate, which
  11. customwas collected
  12. washwashed with water
  13. customair-dried
  14. custompurified
  15. additiona mixture of 5% ethyl acetate
  16. additionFractions containing the product
  17. customtriturated with ether

Sources & evidence

ORD record
ord-42d05974c47b4ae4ac44fa430786a08a
Source dataset
uspto-grants-1985_02
Patent number
US04500708

Reaction notes

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