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

HRID 615706Notes

Reaction equation

HRID 615706 reaction equation
[CH3:1][CH:2]([CH2:6][CH2:7][CH2:8][CH3:9])[C:3]([OH:5])=[O:4].S(Cl)(Cl)=O.CCCCCC.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[S:29][C:28]3=[CH:30][N:31]([CH2:42]O)[C:32](=[O:41])[C:33]([C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=4)=[C:27]3[NH:26][C:25]=2[CH:44]=1>N1C=CC=CC=1>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[S:29][C:28]3=[CH:30][N:31]([CH2:42][O:4][C:3](=[O:5])[CH:2]([CH3:1])[CH2:6][CH2:7][CH2:8][CH3:9])[C:32](=[O:41])[C:33]([C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=4)=[C:27]3[NH:26][C:25]=2[CH:44]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 206532-Methylhexanoic AcidHCID 24386Thionyl ChlorideHCID 204269037-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one

Product 1

HCID 204268967-chloro-4-(4-chlorophenyl)-2-[(2-methyl-1-oxohexyloxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-oneYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 1.4 g. of 2-methylhexanoic acid (10.8 mmol.) and 3 ml. of thionyl chloride (41.1 mmol.) in 20 ml. of Skellysolve B was refluxed on a steam bath for five hours. The mixture was then concentrated under reduced pressure and the residue azeotroped twice with 30 ml. of cyclohexane to yield a colorless oil. The oil was then 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 20 ml. of pyridine. After stirring for 35 minutes, the reaction mixture was poured onto ice-water and allowed to stand for 16 hours at room temperature, resulting in formation of a yellow solid, which was collected, washed with water, air-dried, then purified using flash chromatography on silica gel, employing a mixture of 2% ethyl acetate: 98% methylene chloride as the eluent. Fractions containing the product were combined and triturated with ether to yield 7-chloro-4-(4-chlorophenyl)-2-[(2-methyl-1-oxohexyloxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a yellow crystalline solid (1.17 g; 76% yield) having the structural formula, ##STR19## a melting point in the range of 140°-146° C. and the following elemental analysis:

Workup

  1. additionA mixture of 1.4 g
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. customthe residue azeotroped twice with 30 ml
  4. customof cyclohexane to yield a colorless oil
  5. additionThe oil was then added dropwise to a cold
  6. additionsuspension of 1.2 g
  7. stirringAfter stirring for 35 minutes
  8. additionthe reaction mixture was poured onto ice-water
  9. customresulting in formation of a yellow solid, which
  10. customwas collected
  11. washwashed with water
  12. customair-dried
  13. custompurified
  14. additiona mixture of 2% ethyl acetate
  15. additionFractions containing the product
  16. customtriturated with ether

Sources & evidence

ORD record
ord-8e9a4912e7f443f3bc28c20e9db869ae
Source dataset
uspto-grants-1985_02
Patent number
US04500708

Reaction notes

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