Reaktion #160197

Reaktionsgleichung

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

Ausbeute 62.1%

Lösungsmittel

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was heated
2. 2
   Temperaturat reflux for 1 hour
3. 3
   SonstigeThe excess solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
5. 5
   Temperaturheated
6. 6
   Temperaturat reflux for 20 minutes
7. 7
   Filtrationfiltered
8. 8
   Sonstigepurified by Waters mass
9. 9
   EinengenThe desired fractions were concentrated to dryness
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    Waschenwashed with 1M NaOH
12. 12
    TrocknenThe combined organics were dried over Na2SO4
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated in vacuo

Vorschrift

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)

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