반응 #160197

반응 방정식

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

수율 62.1%

용매

DCE

반응 조건

후처리

1. 1
   온도the reaction mixture was heated
2. 2
   온도at reflux for 1 hour
3. 3
   기타The excess solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
5. 5
   온도heated
6. 6
   온도at reflux for 20 minutes
7. 7
   여과filtered
8. 8
   기타purified by Waters mass
9. 9
   농축The desired fractions were concentrated to dryness
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    세척washed with 1M NaOH
12. 12
    건조The combined organics were dried over Na2SO4
13. 13
    여과filtered
14. 14
    농축concentrated in vacuo

실험 절차

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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