Ethanol → Pentoxazone

HRID 2289023Notes

Reaction equation

HRID 2289023 reaction equation
[CH2:1](N(CCCC)CCCC)[CH2:2][CH2:3]C.[Cl:14][C:15]1[C:20]([O:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:19][C:18]([NH:27][C:28](=[O:32])[O:29][CH2:30][CH3:31])=[C:17]([F:33])[CH:16]=1.[OH:34]C(C(C)=C)C(OCC)=O.C(O)C>CCCCCC.C1(C)C=CC=CC=1>[Cl:14][C:15]1[C:20]([O:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26]2)=[CH:19][C:18]([N:27]2[C:31](=[O:34])[C:30](=[C:2]([CH3:3])[CH3:1])[O:29][C:28]2=[O:32])=[C:17]([F:33])[CH:16]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 7622TributylamineHCID 108555893-Butenoic acid, 2-hydroxy-3-methyl-, ethyl esterHCID 11033971N-[4-Chloro-5-(cyclopentyloxy)-2-fluorophenyl]carbamic acid ethyl ester

Product 1

HCID 11714234PentoxazoneYield 850.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Conditions

Temperature
200 °C

Procedure

Ferric chloride hexahydrate (2.7 g, 0.01 mol), tributylamine (9.3 g, 0.05 mol) and ethyl N-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)carbamate (151 g, 0.5 mol) were introduced into a three-necked flask (1 L) equipped with a mechanical stirrer and a Dean Stark, and the resulting mixture was heated to 200° C. with stirring to form a homogeneous solution. Then, ethyl 2-hydroxy-3-methyl-3-butenoate (108 g, 0.75 mol) was added dropwise over 4.8 hours, and after the addition, the solution was stirred for another 2 hours. The ethanol generated during the heating and stirring was distilled away by means of the Dean Stark. After completion of the reaction, the reaction mixture was allowed to cool to about 100° C., and then toluene (500 mL) was added to form a solution. The solution was washed with 1N hydrochloric acid (250 mL) and water (250 mL). The organic layer was concentrated under reduced pressure, and the resulting oily crude product was crystallized in ethanol (200 mL) acidified with sulfuric acid. The precipitated crystals were collected by filtration and washed with a small amount of acidic ethanol and then hexane to obtain 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (150.5 g, yield 85.1%) as white crystals.

Workup

  1. customequipped with a mechanical stirrer
  2. customto form a homogeneous solution
  3. additionafter the addition
  4. stirringthe solution was stirred for another 2 hours
  5. stirringstirring
  6. distillationwas distilled away by means of the Dean Stark
  7. customAfter completion of the reaction
  8. temperatureto cool to about 100° C.
  9. customto form a solution
  10. washThe solution was washed with 1N hydrochloric acid (250 mL) and water (250 mL)
  11. concentrationThe organic layer was concentrated under reduced pressure
  12. customthe resulting oily crude product was crystallized in ethanol (200 mL)
  13. filtrationThe precipitated crystals were collected by filtration
  14. washwashed with a small amount of acidic ethanol

Sources & evidence

ORD record
ord-4f93b08f011d4783844150d8dee9f68d
Source dataset
uspto-grants-2000_07
Patent number
US06090946

Reaction notes

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