Réaction #160197

Équation de réaction

1-Chloroethyl carbonochloridate

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

→

[10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Rendement 62.1%

Solvants

DCE

Conditions de réaction

Traitement

1. 1
   Températurethe reaction mixture was heated
2. 2
   Températureat reflux for 1 hour
3. 3
   AutreThe excess solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
5. 5
   Températureheated
6. 6
   Températureat reflux for 20 minutes
7. 7
   Filtrationfiltered
8. 8
   Autrepurified by Waters mass
9. 9
   ConcentrationThe desired fractions were concentrated to dryness
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    Lavagewashed with 1M NaOH
12. 12
    SéchageThe combined organics were dried over Na2SO4
13. 13
    Filtrationfiltered
14. 14
    Concentrationconcentrated in vacuo

Mode opératoire

1-Chloroethyl carbonochloridate (142 mg, 108 μL, 0.99 mmol) was added to a solution of [8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (44 mg, 0.08 mmol) in DCE (508 μL) at room temperature and then the reaction mixture was heated at reflux for 1 hour. The excess solvent was removed in vacuo and the carbamate intermediate was dissolved in MeOH (2 mL) and heated at reflux for 20 minutes. The reaction mixture was cooled to room temperature, filtered and purified by Waters mass directed LC/MS-HPLC: (1-99% ACN/H2O (5 mM HCl)). The desired fractions were concentrated to dryness, dissolved in EtOAc and washed with 1M NaOH. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to yield [10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (22 mg, 60%). ESI-MS m/z calc. 442.2. Found 443.5 (M+1)+; Retention time: 1.51 minutes (3 min run)

Source