Reacción #160221

Ecuación de reacción

1-chloroethyl chloroformate

1-chloroethyl chloroformate

[8-benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

1-chloroethyl chloroformate

→

(4-isopropoxy-3-methyl-phenyl)-[10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt

Rendimiento 47.8%

Disolventes

DCE

DCE

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe reaction mixture was heated to reflux
2. 2
   Temperaturathe reaction mixture was heated
3. 3
   Temperaturato reflux for a further 8 hours
4. 4
   workup.WAITAfter 8 hours
5. 5
   Temperaturathe reaction mixture was heated
6. 6
   Temperaturato reflux for a further 15 hours
7. 7
   OtroThe excess solvent was removed under reduced pressure
8. 8
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
9. 9
   Temperaturaheated
10. 10
    Temperaturaat reflux for 1 hour
11. 11
    Filtraciónfiltered
12. 12
    Otropurified by Waters mass

Procedimiento

A solution of 1-chloroethyl chloroformate (89 μL, 0.80 mmol) in DCE (0.1 mL) was added to a stirred solution of [8-benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (67 mg, 0.13 mmol) in DCE (488 μL) under an atmosphere of nitrogen and the reaction mixture was heated to reflux. After 1 hour, an additional aliquot of 1-chloroethyl chloroformate (89 μL, 0.80 mmol) was added and the reaction mixture was heated to reflux for a further 8 hours. After 8 hours, an additional 1-chloroethyl chloroformate (89 μL, 0.80 mmol) was added and the reaction mixture was heated to reflux for a further 15 hours. The excess solvent was removed under reduced pressure and the carbamate intermediate was dissolved in MeOH (2 mL) and heated at reflux for 1 hour. The reaction mixture was cooled to room temperature, filtered and purified by Waters mass directed LC/MS-HPLC: (10-99% ACN/H2O (5 mM HCl)) to afford (4-isopropoxy-3-methyl-phenyl)-[10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt (28 mg, 47%). ESI-MS m/z calc. 414.2. Found 415.7 (M+1)+; Retention time: 1.54 minutes (3 min run).

Fuente