反応 #160197

反応方程式

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

収率 62.1%

溶媒

DCE

反応条件

後処理

1. 1
   温度the reaction mixture was heated
2. 2
   温度at reflux for 1 hour
3. 3
   その他The excess solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
5. 5
   温度heated
6. 6
   温度at reflux for 20 minutes
7. 7
   ろ過filtered
8. 8
   その他purified by Waters mass
9. 9
   濃縮The desired fractions were concentrated to dryness
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    洗浄washed with 1M NaOH
12. 12
    乾燥The combined organics were dried over Na2SO4
13. 13
    ろ過filtered
14. 14
    濃縮concentrated in vacuo

実験手順

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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