Acetone → 4-(Octanoyloxy)methoxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide

HRID 1583305Notes

Reaction equation

HRID 1583305 reaction equation
[CH3:1][N:2]1[S:11](=[O:13])(=[O:12])[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]([OH:14])=[C:3]1[C:15]([NH:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][N:23]=1)=[O:16].C(=O)([O-])[O-].[K+].[K+].[C:30]([O:39][CH2:40]Cl)(=[O:38])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].CC(C)=O>C1(C)C=CC=CC=1.CCCCCC>[C:30]([O:39][CH2:40][O:14][C:4]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=2[S:11](=[O:13])(=[O:12])[N:2]([CH3:1])[C:3]=1[C:15]([NH:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][N:23]=1)=[O:16])(=[O:38])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]

Participants

6

Reactant 4

HCID 180AcetoneHCID 11430Potassium Carbonate2×HCID 525231Chloromethyl octanoate2×HCID 54676228Piroxicam

Product 1

HCID 135066554-(Octanoyloxy)methoxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide

Reagents, catalysts & solvents 1

HCID 21889329Toluene hexaneSolvent

Procedure

To a round bottomed flask equipped with a reflux condenser and a stirring bar were added piroxicam (1.00 g, 3.0 mmol), potassium carbonate (840 mg, 6.0 mmol), chloromethyl octanoate (870 mg, 4.5 mmol) and acetone (15 mL). The heterogenous reaction mixture was heated to reflux under a nitrogen atmosphere. After 6 hours additional chloromethyl octanoate (250 mg, 0.75 mmol) and additional potassium carbonate (210 mg, 1.5 mmol) were added and reflux continued for an additional hour. Chromatographed title product was isolated, according to the method of Example 5, as a yellow foam which oiled from toluene/hexane, but crystallized from the oil upon refrigeration (690 mg white crystals, 1.4 mmol, 47%); mp 98°-99° C.; IR (KBr) 1766, 1683 cm-1 ; 1H NMR (CDCl3) delta 0.87 (t, J=8 Hz, 3H), 1.02-1.48 (m, 10H), 2.19 (t, J=6 Hz, 2 H), 3.12 (s, 3H), 5.70 (s, 2H), 7.08-7.17 (m, 1H), 7.67-7.98 (m, 5H), 8.30-8.45 (m, 2H), 9.32 (br s, 1H); precise mass calcd for C24H30N3O6S m/e (P+ +H) 488.1859, found 488.1794.

Workup

  1. customTo a round bottomed flask equipped with a reflux condenser and a stirring bar
  2. temperatureThe heterogenous reaction mixture was heated
  3. temperatureto reflux under a nitrogen atmosphere
  4. temperaturereflux
  5. waitcontinued for an additional hour
  6. customChromatographed title product
  7. customwas isolated
  8. customcrystallized from the oil upon refrigeration (690 mg white crystals, 1.4 mmol, 47%)

Sources & evidence

ORD record
ord-2b3f3e5e48df47deadb68a8e44b9094d
Source dataset
uspto-grants-1985_11
Patent number
US04551452

Reaction notes

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