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

HRID 615707Notes

Reaction equation

HRID 615707 reaction equation
[CH3:1][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].S(Cl)(Cl)=O.C1CCCCC1.[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]([CH3:8])[CH3:7])[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 8078CyclohexaneHCID 24386Thionyl ChlorideHCID 266082,3-Dimethylbutanoic acidHCID 204269037-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one

Product 1

HCID 204268997-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxobutoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-oneYield 11%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 1.0 g. of 2,3-dimethylbutyric acid (8.6 mmol.) and 2.5 ml. of thionyl chloride (34.3 mmol.) in 10 ml. of cyclohexane was refluxed on a steam bath for 1.5 hours. The resulting solution was then concentrated under reduced pressure and the residue azeotroped with cyclohexane to yield a colorless oil. The oil was then added dropwise to a cold, stirred suspension containing 0.8 g. of 7-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one (2.0 mmol.) in 15 ml. of pyridine. After stirring for 35 minutes, the mixture was poured onto ice-water, resulting in the formation of a yellow precipitate which was filtered, washed with water and 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-oxobutoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a yellow crystalline solid (110 mg; 11% yield) having the structural formula, ##STR20## a melting point in the range of 204°-205° C. and the following elemental analysis:

Workup

  1. additionA mixture of 1.0 g
  2. concentrationThe resulting solution was then concentrated under reduced pressure
  3. customthe residue azeotroped with cyclohexane
  4. customto yield a colorless oil
  5. additionThe oil was then added dropwise to a cold
  6. additioncontaining 0.8 g
  7. stirringAfter stirring for 35 minutes
  8. additionthe mixture was poured onto ice-water
  9. customresulting in the formation of a yellow precipitate which
  10. filtrationwas filtered
  11. washwashed with water
  12. customair-dried
  13. custompurified
  14. additiona mixture of 5% ethyl acetate
  15. additionFractions containing the product
  16. customtriturated with ether

Sources & evidence

ORD record
ord-b6836401df0444ee8dfce4b7fe15c1e1
Source dataset
uspto-grants-1985_02
Patent number
US04500708

Reaction notes

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